Neuroscience › Developmental Neuroscience

Neurogenesis and neuroplasticity mechanisms

Works Count: 39598

Wikipedia

Description

This cluster of papers explores the phenomenon of adult neurogenesis, focusing on the generation, differentiation, and functional implications of new neurons and glial cells in the mammalian brain. It covers various aspects such as the role of neurogenesis in brain development, neuronal replacement, synaptic plasticity, cognitive function, and the potential therapeutic applications for neurological disorders.

Keywords

Neurogenesis; Adult Stem Cells; Brain Development; Neuronal Differentiation; Hippocampal Neurogenesis; Oligodendrocyte Progenitors; Neural Stem Cells; Glia and Neurons; Cortical Development; Neurogenic Niches

Neurons derived from radial glial cells establish radial units in neocortex

2001-02-01

Stephen C. Noctor , Alexander C. Flint , Tamily A. Weissman +2 more

Learning enhances adult neurogenesis in the hippocampal formation

1999-03-01

Elizabeth Gould , Anna V. Beylin , Patima Tanapat +2 more

Turning Blood into Brain: Cells Bearing Neuronal Antigens Generated in Vivo from Bone Marrow

2000-12-01

Éva Mezey , Karen J. Chandross , G Harta +2 more

Bone marrow stem cells give rise to a variety of hematopoietic lineages and repopulate the blood throughout adult life. We show that, in a strain of mice incapable of developing … Bone marrow stem cells give rise to a variety of hematopoietic lineages and repopulate the blood throughout adult life. We show that, in a strain of mice incapable of developing cells of the myeloid and lymphoid lineages, transplanted adult bone marrow cells migrated into the brain and differentiated into cells that expressed neuron-specific antigens. These findings raise the possibility that bone marrow-derived cells may provide an alternative source of neurons in patients with neurodegenerative diseases or central nervous system injury.

Neurogenesis in the adult is involved in the formation of trace memories

2001-03-15

Tracey J. Shors , George R. Miesegaes , Anna V. Beylin +3 more

Cellular Composition and Three-Dimensional Organization of the Subventricular Germinal Zone in the Adult Mammalian Brain

1997-07-01

Fiona Doetsch , José Manuel García‐Verdugo , Arturo Álvarez-Buylla

The adult mammalian subventricular zone (SVZ) contains stem cells that give rise to neurons and glia. In vivo , SVZ progeny migrate 3–8 mm to the olfactory bulb, where they … The adult mammalian subventricular zone (SVZ) contains stem cells that give rise to neurons and glia. In vivo , SVZ progeny migrate 3–8 mm to the olfactory bulb, where they form neurons. We show here that the SVZ of the lateral wall of the lateral ventricles in adult mice is composed of neuroblasts, glial cells, and a novel putative precursor cell. The topographical organization of these cells suggests how neurogenesis and migration are integrated in this region. Type A cells had the ultrastructure of migrating neuronal precursors. These cells were arranged as chains parallel to the walls of the ventricle and were polysialylated neural adhesion cell molecule- (PSA–NCAM), TuJ1- (β-tubulin), and nestin-positive but GFAP- and vimentin-negative. Chains of Type A cells were ensheathed by two ultrastructurally distinct astrocytes (Type B1 and B2) that were GFAP-, vimentin-, and nestin-positive but PSA–NCAM- and TuJ1-negative. Type A and B2 (but not B1) cells incorporated [ 3 H]thymidine. The most actively dividing cell in the SVZ corresponded to Type C cells, which had immature ultrastructural characteristics and were nestin-positive but negative to the other markers. Type C cells formed focal clusters closely associated with chains of Type A cells. Whereas Type C cells were present throughout the SVZ, they were not found in the rostral migratory stream that links the SVZ with the olfactory bulb. These results suggest that chains of migrating neuroblasts in the SVZ may be derived from Type C cells. Our results provide a topographical model for the adult SVZ and should serve as a basis for the in vivo identification of stem cells in the adult mammalian brain.

View PDF Chat

The establishment of polarity by hippocampal neurons in culture

1988-04-01

Carlos G. Dotti , CA Sullivan , GA Banker

By the end of the first week in culture, hippocampal neurons have established a single axon and several dendrites. These 2 classes of processes differ in their morphology, in their … By the end of the first week in culture, hippocampal neurons have established a single axon and several dendrites. These 2 classes of processes differ in their morphology, in their molecular composition, and in their synaptic polarity (Bartlett and Banker, 1984a, b; Caceres et al., 1984). We examined the events during the first week in culture that lead to the establishment of this characteristic form. Hippocampal cells were obtained from 18 d fetal rats, plated onto polylysine-treated coverslips, and maintained in a serum-free medium. The development of individual cells was followed by sequential photography at daily intervals until both axons and dendrites had been established; identification of the processes was confirmed by immunostaining for MAP2, a dendritic marker. Time-lapse video recording was used to follow the early stages of process formation. Hippocampal neurons acquired their characteristic form by a stereotyped sequence of developmental events. The cells first established several, apparently identical, short processes. After several hours, one of the short processes began to grow very rapidly; it became the axon. The remaining processes began to elongate a few days later and grew at a much slower rate. They became the cell's dendrites. Neurons that arose following mitosis in culture underwent this same sequence of developmental events. In a few instances, 2 processes from a cell exhibited the rapid growth typical of axons, but only one maintained this growth; the other retracted and became a dendrite. Axons branched primarily by the formation of collaterals, not by bifurcation of growth cones. As judged by light microscopy, processes are not specified as axons or dendrites when they arise. The first manifestation of neuronal polarity is the acquisition of axonal characteristics by one of the initial processes; subsequently the remaining processes become dendrites.

View PDF Chat

Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice

2005-09-21

Henriette van Praag , Tiffany E. Shubert , Chunmei Zhao +1 more

Aging causes changes in the hippocampus that may lead to cognitive decline in older adults. In young animals, exercise increases hippocampal neurogenesis and improves learning. We investigated whether voluntary wheel … Aging causes changes in the hippocampus that may lead to cognitive decline in older adults. In young animals, exercise increases hippocampal neurogenesis and improves learning. We investigated whether voluntary wheel running would benefit mice that were sedentary until 19 months of age. Specifically, young and aged mice were housed with or without a running wheel and injected with bromodeoxyuridine or retrovirus to label newborn cells. After 1 month, learning was tested in the Morris water maze. Aged runners showed faster acquisition and better retention of the maze than age-matched controls. The decline in neurogenesis in aged mice was reversed to 50% of young control levels by running. Moreover, fine morphology of new neurons did not differ between young and aged runners, indicating that the initial maturation of newborn neurons was not affected by aging. Thus, voluntary exercise ameliorates some of the deleterious morphological and behavioral consequences of aging.

View PDF Chat

Functional neurogenesis in the adult hippocampus

2002-02-01

Henriette van Praag , Alejandro F. Schinder , Brian R. Christie +3 more

From Marrow to Brain: Expression of Neuronal Phenotypes in Adult Mice

2000-12-01

Timothy R. Brazelton , Fábio Rossi , Gilmor I. Keshet +1 more

After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) developed in the central nervous system. Flow … After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) developed in the central nervous system. Flow cytometry revealed a population of donor-derived cells in the brain with characteristics distinct from bone marrow. Confocal microscopy of individual cells showed that hundreds of marrow-derived cells in brain sections expressed gene products typical of neurons (NeuN, 200-kilodalton neurofilament, and class III β-tubulin) and were able to activate the transcription factor cAMP response element–binding protein (CREB). The generation of neuronal phenotypes in the adult brain 1 to 6 months after an adult bone marrow transplant demonstrates a remarkable plasticity of adult tissues with potential clinical applications.

Stress, Depression, and Neuroplasticity: A Convergence of Mechanisms

2007-09-12

Christopher Pittenger , Ronald S. Duman

View PDF Chat

Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats

1965-06-01

Joseph Altman , Gopal D. Das

Abstract In the autoradiograms of young rats injected with thymidine‐H 3 many of the granule cells of the dentate gyrus were found labeled. The number of labeled cells declined rapidly … Abstract In the autoradiograms of young rats injected with thymidine‐H 3 many of the granule cells of the dentate gyrus were found labeled. The number of labeled cells declined rapidly with increased age at the time of injection. Histological studies showed the presence in young rats of a large germinal matrix of mitotic cells in the ependymal and subependymal layers of the third and lateral ventricles. The areal extent and cell population of this germinal pool declined rapidly from birth on, with a transient rise with a peak at about 15 days. During this latter period the number of “undifferentiated” cells near the granular layer of the dentate gyrus showed a rapid rise with a subsequent decline. The decline in the number of “undifferentiated” cells was accompanied by a rise in the number of differentiated granule cells. Cell counts in homologous parts of the dentate gyrus indicated a six‐fold increase in the number of differentiated granule cells from birth to three months. We postulated that undifferentiated cells migrate postnatally from the forebrain ventricles to the hippocampus where they become differentiated. The possible functional significance of delayed hippocampal neurogenesis is discussed with reference to our finding of incorporation of testosterone‐H 3 by cells of the hippocampus, implicating that they may function as receptors of gonadal hormones.

A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium

1983-06-01

Martin Raff , Robert H. Miller , Mark Noble

The cell biology of neurogenesis

2005-10-01

Magdalena Götz , Wieland Β. Huttner

Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus

1999-03-01

Henriette van Praag , Gerd Kempermann , Fred H. Gage

Long-Distance Neuronal Migration in the Adult Mammalian Brain

1994-05-20

Carlos Lois , Arturo Álvarez-Buylla

During the development of the mammalian brain, neuronal precursors migrate to their final destination from their site of birth in the ventricular and subventricular zones (VZ and SVZ, respectively). SVZ … During the development of the mammalian brain, neuronal precursors migrate to their final destination from their site of birth in the ventricular and subventricular zones (VZ and SVZ, respectively). SVZ cells in the walls of the lateral ventricle continue to proliferate in the brain of adult mice and can generate neurons in vitro, but their fate in vivo is unknown. Here SVZ cells from adult mice that carry a neuronal-specific transgene were grafted into the brain of adult recipients. In addition, the fate of endogenous SVZ cells was examined by microinjection of tritiated thymidine or a vital dye that labeled a discrete population of SVZ cells. Grafted and endogenous SVZ cells in the lateral ventricle of adult mice migrate long distances and differentiate into neurons in the olfactory bulb.

Running enhances neurogenesis, learning, and long-term potentiation in mice

1999-11-09

Henriette van Praag , Brian R. Christie , Terrence J. Sejnowski +1 more

Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups … Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning.

View PDF Chat

New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory?

2010-03-31

Wei Deng , James B. Aimone , Fred H. Gage

View PDF Chat

Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone

1993-07-01

Maria B. Luskin

Vascular niche for adult hippocampal neurogenesis

2000-01-01

Theo D. Palmer , Andrew R. Willhoite , Fred H. Gage

The thin lamina between the hippocampal hilus and granule cell layer, or subgranule zone (SGZ), is an area of active proliferation within the adult hippocampus known to generate new neurons … The thin lamina between the hippocampal hilus and granule cell layer, or subgranule zone (SGZ), is an area of active proliferation within the adult hippocampus known to generate new neurons throughout adult life. Although the neuronal fate of many dividing cells is well documented, little information is available about the phenotypes of cells in S-phase or how the dividing cells might interact with neighboring cells in the process of neurogenesis. Here, we make the unexpected observation that dividing cells are found in dense clusters associated with the vasculature and roughly 37% of all dividing cells are immunoreactive for endothelial markers. Most of the newborn endothelial cells disappear over several weeks, suggesting that neurogenesis is intimately associated with a process of active vascular recruitment and subsequent remodeling. The present data provide the first evidence that adult neurogenesis occurs within an angiogenic niche. This environment may provide a novel interface where mesenchyme-derived cells and circulating factors influence plasticity in the adult central nervous system. J. Comp. Neurol. 425:479–494, 2000. © 2000 Wiley-Liss, Inc.

Mechanisms and Functional Implications of Adult Neurogenesis

2008-02-01

Chunmei Zhao , Wei Deng , Fred H. Gage

Preparation of separate astroglial and oligodendroglial cell cultures from rat cerebral tissue.

1980-06-01

Ken D. McCarthy , Jean de Vellis

A novel method has been developed for the preparation of nearly pure separate cultures of astrocytes and oligodendrocytes. The method is based on (a) the absence of viable neurons in … A novel method has been developed for the preparation of nearly pure separate cultures of astrocytes and oligodendrocytes. The method is based on (a) the absence of viable neurons in cultures prepared from postnatal rat cerebra, (b) the stratification of astrocytes and oligodendrocytes in culture, and (c) the selective detachment of the overlying oligodendrocytes when exposed to sheer forces generated by shaking the cultures on an orbital shaker for 15--18 h at 37 degrees C. Preparations appear greater than 98% pure and contain approximately 1-2 x 10(7) viable cells (20--40 mg of cell protein). Three methods were used to characterize these two culture t ypes. First, electron microscopic examination was used to identify the cells in each preparation (mixed and separated cultures of astrocytes and oligodendrocytes) and to assess the purity of each preparation. Second, two oligodendroglial cell markers, 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 3.1.4.37) and glycerol phosphate dehydrogenase (EC 1.1.1.8) were monitored. Third, the regulation of cyclic AMP accumulation in each culture type was examined. In addition to these studies, we examined the influence of brain extract and dibutyryl cAMP on the gross morphology and ultrastructure of each preparation. These agents induced astroglial process formation without any apparent morphological effect on oligodendrocytes. Collectively, the results indicate that essentially pure cultures of astrocytes and of oligodendrocytes can be prepared and maintained. These preparations should significantly aid in efforts to examine the biochemistry, physiology, and pharmacology of these two major classes of central nervous system cells.

View PDF Chat

Direct isolation of human central nervous system stem cells

2000-12-19

Nobuko Uchida , David Buck , Dongping He +6 more

Stem cells, which are clonogenic cells with self-renewal and multilineage differentiation properties, have the potential to replace or repair damaged tissue. We have directly isolated clonogenic human central nervous system … Stem cells, which are clonogenic cells with self-renewal and multilineage differentiation properties, have the potential to replace or repair damaged tissue. We have directly isolated clonogenic human central nervous system stem cells (hCNS-SC) from fresh human fetal brain tissue, using antibodies to cell surface markers and fluorescence-activated cell sorting. These hCNS-SC are phenotypically 5F3 (CD133)(+), 5E12(+), CD34(-), CD45(-), and CD24(-/lo). Single CD133(+) CD34(-) CD45(-) sorted cells initiated neurosphere cultures, and the progeny of clonogenic cells could differentiate into both neurons and glial cells. Single cells from neurosphere cultures initiated from CD133(+) CD34(-) CD45(-) cells were again replated as single cells and were able to reestablish neurosphere cultures, demonstrating the self-renewal potential of this highly enriched population. Upon transplantation into brains of immunodeficient neonatal mice, the sorted/expanded hCNS-SC showed potent engraftment, proliferation, migration, and neural differentiation.

View PDF Chat

Neurogenesis in the adult human hippocampus

1998-11-01

Peter S. Eriksson , Ekaterina Perfilieva , Thomas Björk‐Eriksson +4 more

View PDF Chat

Mode of cell migration to the superficial layers of fetal monkey neocortex

1972-05-01

Pasko Rakić

Abstract Golgi and electronmicroscopic methods were used to define the shapes and intercellular relationships of cells migrating from their sites of origin near the ventricular surface across the intermediate zone … Abstract Golgi and electronmicroscopic methods were used to define the shapes and intercellular relationships of cells migrating from their sites of origin near the ventricular surface across the intermediate zone to the superficial neocortical layers of the parietooccipital region in the brains of 75‐ to 97‐day monkey fetuses. After mitotic division in either ventricular or subventricular zones, the cells enter the intermediate zone and assume an elongated bipolar form oriented toward the cortical plate. The leading processes, 50 to 70 μ long, are irregular cytoplasmic cylinders containing prominent Golgi apparatus, mitochondria, microtubules, ribosomal rosettes, immature endoplasmic reticulum and occasional centrioles. They usually terminate in several attenuated expansions, the longest one oriented toward the cortical plate. The trailing processes are more slender, relatively uniform in caliber and display few organelles. Throughout the 3500 μ pathway across the intermediate zone the migrating cells are apposed to elongated, radially oriented, immature glial processes which span the full thickness of the cerebral wall. Most of the perikarya of these glial cells in the younger specimens lie in the ventricular or subventricular zones, but in older fetuses of this series many are found in the intermediate zone. The main characteristics of these fibers are: elongated cylindrical form contaiing numerous microtubules; electronlucent cytoplasmic matrix; short lamellate expansions protruding at right angles from the segment of the fiber which runs through the intermediate zone; and terminal endfeet joined at the pial surface to form a continuous sheet coated externally with basement membrane. It is suggested that glial radial fibers provide guidelines for cell migration through the complex mixture of closely packed cell processes and cell bodies that compose the developing cerebral wall. Strong surface affinity between radial fiber and migrating cell is suggested in regions where both follow precisely the same curving course from subventricular to intermediate zones and also in areas where large extracellular spaces separate other cells and processes but in which migrating cells and radial fibers remain closely paired nonetheless. Specific affinity between them is implied in the failure of migrating cells to follow any of the myriad differently‐oriented processes they encounter. Several generations of postmitotic cells appear to migrate along the same radial fiber, a developmental mechanism that would allow for the vertical cell columns of adult neocortex.

More hippocampal neurons in adult mice living in an enriched environment

1997-04-01

Gerd Kempermann , H. Georg Kuhn , Fred H. Gage

Generation of Neurons and Astrocytes from Isolated Cells of the Adult Mammalian Central Nervous System

1992-03-27

Brent A. Reynolds , Samuel Weiss

Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few … Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for γ-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes.

Mammalian Neural Stem Cells

2000-02-25

Fred H. Gage

Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells can also … Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells can also be derived from more primitive embryonic stem cells. The location of the adult stem cells and the brain regions to which their progeny migrate in order to differentiate remain unresolved, although the number of viable locations is limited in the adult. The mechanisms that regulate endogenous stem cells are poorly understood. Potential uses of stem cells in repair include transplantation to repair missing cells and the activation of endogenous cells to provide “self-repair.” Before the full potential of neural stem cells can be realized, we need to learn what controls their proliferation, as well as the various pathways of differentiation available to their daughter cells.

A Neurotrophic Model for Stress-Related Mood Disorders

2006-04-25

Ronald S. Duman , Lisa M. Monteggia

Exercise: a behavioral intervention to enhance brain health and plasticity

2002-06-01

Carl W. Cotman

View PDF Chat

The Basics of Brain Development

2010-11-02

Joan Stiles , Terry L. Jernigan

Over the past several decades, significant advances have been made in our understanding of the basic stages and mechanisms of mammalian brain development. Studies elucidating the neurobiology of brain development … Over the past several decades, significant advances have been made in our understanding of the basic stages and mechanisms of mammalian brain development. Studies elucidating the neurobiology of brain development span the levels of neural organization from the macroanatomic, to the cellular, to the molecular. Together this large body of work provides a picture of brain development as the product of a complex series of dynamic and adaptive processes operating within a highly constrained, genetically organized but constantly changing context. The view of brain development that has emerged from the developmental neurobiology literature presents both challenges and opportunities to psychologists seeking to understand the fundamental processes that underlie social and cognitive development, and the neural systems that mediate them. This chapter is intended to provide an overview of some very basic principles of brain development, drawn from contemporary developmental neurobiology, that may be of use to investigators from a wide range of disciplines.

View PDF Chat

ADULT NEUROGENESIS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM

2005-03-18

Guo‐li Ming , Hongjun Song

Forty years since the initial discovery of neurogenesis in the postnatal rat hippocampus, investigators have now firmly established that active neurogenesis from neural progenitors continues throughout life in discrete regions … Forty years since the initial discovery of neurogenesis in the postnatal rat hippocampus, investigators have now firmly established that active neurogenesis from neural progenitors continues throughout life in discrete regions of the central nervous systems (CNS) of all mammals, including humans. Significant progress has been made over the past few years in understanding the developmental process and regulation of adult neurogenesis, including proliferation, fate specification, neuronal maturation, targeting, and synaptic integration of the newborn neurons. The function of this evolutionarily conserved phenomenon, however, remains elusive in mammals. Adult neurogenesis represents a striking example of structural plasticity in the mature CNS environment. Advances in our understanding of adult neurogenesis will not only shed light on the basic principles of adult plasticity, but also may lead to strategies for cell replacement therapy after injury or degenerative neurological diseases.

Cancerous stem cells can arise from pediatric brain tumors

2003-11-26

Houman D. Hemmati , Ichiro Nakano , Jorge A. Lazareff +4 more

Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain … Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain tumors, including medulloblastomas and gliomas, contain cells with properties similar to neural stem cells. We find that tumor-derived progenitors form neurospheres that can be passaged at clonal density and are able to self-renew. Under conditions promoting differentiation, individual cells are multipotent, giving rise to both neurons and glia, in proportions that reflect the tumor of origin. Unlike normal neural stem cells, however, tumor-derived progenitors have an unusual capacity to proliferate and sometimes differentiate into abnormal cells with multiple differentiation markers. Gene expression analysis reveals that both whole tumors and tumor-derived neurospheres express many genes characteristic of neural and other stem cells, including CD133, Sox2 , musashi-1, bmi-1 , maternal embryonic leucine zipper kinase, and phosphoserine phosphatase, with variation from tumor to tumor. After grafting to neonatal rat brains, tumor-derived neurosphere cells migrate, produce neurons and glia, and continue to proliferate for more than 4 weeks. The results show that pediatric brain tumors contain neural stem-like cells with altered characteristics that may contribute to tumorigenesis. This finding may have important implications for treatment by means of specific targeting of stem-like cells within brain tumors.

View PDF Chat

Biology of Oligodendrocyte and Myelin in the Mammalian Central Nervous System

2001-04-01

Nicole Baumann , Danielle Pham-Dinh

Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, … Oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), and astrocytes constitute macroglia. This review deals with the recent progress related to the origin and differentiation of the oligodendrocytes, their relationships to other neural cells, and functional neuroglial interactions under physiological conditions and in demyelinating diseases. One of the problems in studies of the CNS is to find components, i.e., markers, for the identification of the different cells, in intact tissues or cultures. In recent years, specific biochemical, immunological, and molecular markers have been identified. Many components specific to differentiating oligodendrocytes and to myelin are now available to aid their study. Transgenic mice and spontaneous mutants have led to a better understanding of the targets of specific dys- or demyelinating diseases. The best examples are the studies concerning the effects of the mutations affecting the most abundant protein in the central nervous myelin, the proteolipid protein, which lead to dysmyelinating diseases in animals and human (jimpy mutation and Pelizaeus-Merzbacher disease or spastic paraplegia, respectively). Oligodendrocytes, as astrocytes, are able to respond to changes in the cellular and extracellular environment, possibly in relation to a glial network. There is also a remarkable plasticity of the oligodendrocyte lineage, even in the adult with a certain potentiality for myelin repair after experimental demyelination or human diseases.

Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases

2004-01-01

Stephen C. Noctor , Verónica Martínez‐Cerdeño , Lidija Ivic +1 more

Exercise training increases size of hippocampus and improves memory

2011-01-31

Kirk I. Erickson , Michelle W. Voss , Ruchika Shaurya Prakash +7 more

The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training … The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.

View PDF Chat

Specification of Cerebral Cortical Areas

1988-07-08

Pasko Rakić

How the immense population of neurons that constitute the human cerebral neocortex is generated from progenitors lining the cerebral ventricle and then distributed to appropriate layers of distinctive cytoarchitectonic areas … How the immense population of neurons that constitute the human cerebral neocortex is generated from progenitors lining the cerebral ventricle and then distributed to appropriate layers of distinctive cytoarchitectonic areas can be explained by the radial unit hypothesis. According to this hypothesis, the ependymal layer of the embryonic cerebral ventricle consists of proliferative units that provide a proto-map of prospective cytoarchitectonic areas. The output of the proliferative units is translated via glial guides to the expanding cortex in the form of ontogenetic columns, whose final number for each area can be modified through interaction with afferent input. Data obtained through various advanced neurobiological techniques, including electron microscopy, immunocytochemistry, [ 3 H]thymidine and receptor autoradiography, retrovirus gene transfer, neural transplants, and surgical or genetic manipulation of cortical development, furnish new details about the kinetics of cell proliferation, their lineage relationships, and phenotypic expression that favor this hypothesis. The radial unit model provides a framework for understanding cerebral evolution, epigenetic regulation of the parcellation of cytoarchitectonic areas, and insight into the pathogenesis of certain cortical disorders in humans.

Exercise builds brain health: key roles of growth factor cascades and inflammation

2007-09-01

Carl W. Cotman , Nicole C. Berchtold , Lori‐Ann Christie

Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus

2000-12-15

Jessica E. Malberg , Amelia J. Eisch , Eric J. Nestler +1 more

Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants … Recent studies suggest that stress-induced atrophy and loss of hippocampal neurons may contribute to the pathophysiology of depression. The aim of this study was to investigate the effect of antidepressants on hippocampal neurogenesis in the adult rat, using the thymidine analog bromodeoxyuridine (BrdU) as a marker for dividing cells. Our studies demonstrate that chronic antidepressant treatment significantly increases the number of BrdU-labeled cells in the dentate gyrus and hilus of the hippocampus. Administration of several different classes of antidepressant, but not non-antidepressant, agents was found to increase BrdU-labeled cell number, indicating that this is a common and selective action of antidepressants. In addition, upregulation of the number of BrdU-labeled cells is observed after chronic, but not acute, treatment, consistent with the time course for the therapeutic action of antidepressants. Additional studies demonstrated that antidepressant treatment increases the proliferation of hippocampal cells and that these new cells mature and become neurons, as determined by triple labeling for BrdU and neuronal- or glial-specific markers. These findings raise the possibility that increased cell proliferation and increased neuronal number may be a mechanism by which antidepressant treatment overcomes the stress-induced atrophy and loss of hippocampal neurons and may contribute to the therapeutic actions of antidepressant treatment.

View PDF Chat

Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

2011-05-01

Guo‐li Ming , Hongjun Song

View PDF Chat

Dynamics of Hippocampal Neurogenesis in Adult Humans

2013-06-01

Kirsty L. Spalding , Olaf Bergmann , Kanar Alkass +7 more

View PDF Chat

Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation

1996-03-15

H. Georg Kuhn , Heather Dickinson-Anson , F H Gage

The hippocampus is one of the few areas of the rodent brain that continues to produce neurons postnatally. Neurogenesis reportedly persists in rats up to 11 months of age. Using … The hippocampus is one of the few areas of the rodent brain that continues to produce neurons postnatally. Neurogenesis reportedly persists in rats up to 11 months of age. Using bromodeoxyuridine (BrdU) labeling, the present study confirms that in the adult rat brain, neuronal progenitor cells divide at the border between the hilus and the granule cell layer (GCL). In adult rats, the progeny of these cells migrate into the GCL and express the neuronal markers NeuN and calbindin-D28k. However, neurogenesis was drastically reduced in aged rats. Six-to 27-month-old Fischer rats were injected intraperitoneally with BrdU to detect newborn cells in vivo and to follow their fate in the dentate gyrus. When killed 4–6 weeks after BrdU labeling, 12- to 27- month-old rats exhibited a significant decline in the density of BrdU- positive cells in the granule cell layer compared with 6-month-old controls. Decreased neurogenesis in aging rats was accompanied by reduced immunoreactivity for poly-sialylated neural cell adhesion molecule, a molecule that is involved in migration and process elongation of developing neurons. When animals were killed immediately (12 hr) after BrdU injection, significantly fewer labeled cells were observed in the GCL and adjacent subgranular zone of aged rats, indicative of a decrease in mitotic activity of neuronal precursor cells. The reduced proliferation was not attributable to a general aged- related metabolic impairment, because the density of BrdU-positive cells was not altered in other brain regions with known mitotic activity (e.g., hilus and lateral ventricle wall). The decline in neurogenesis that occurs throughout the lifespan of an animal can thus be related to a decreasing proliferation of granule cell precursors.

View PDF Chat

Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants

2003-08-08

Luca Santarelli , Michael Saxe , Cornelius T. Gross +7 more

Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks … Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.

Dentate Granule Cell Neurogenesis Is Increased by Seizures and Contributes to Aberrant Network Reorganization in the Adult Rat Hippocampus

1997-05-15

Jack M. Parent , Timothy W. Yu , Rebecca T. Leibowitz +3 more

The dentate granule cell layer of the rodent hippocampal formation has the distinctive property of ongoing neurogenesis that continues throughout adult life. In both human temporal lobe epilepsy and rodent … The dentate granule cell layer of the rodent hippocampal formation has the distinctive property of ongoing neurogenesis that continues throughout adult life. In both human temporal lobe epilepsy and rodent models of limbic epilepsy, this same neuronal population undergoes extensive remodeling, including reorganization of mossy fibers, dispersion of the granule cell layer, and the appearance of granule cells in ectopic locations within the dentate gyrus. The mechanistic basis of these abnormalities, as well as their potential relationship to dentate granule cell neurogenesis, is unknown. We used a systemic chemoconvulsant model of temporal lobe epilepsy and bromodeoxyuridine (BrdU) labeling to investigate the effects of prolonged seizures on dentate granule cell neurogenesis in adult rats, and to examine the contribution of newly differentiated dentate granule cells to the network changes seen in this model. Pilocarpine-induced status epilepticus caused a dramatic and prolonged increase in cell proliferation in the dentate subgranular proliferative zone (SGZ), an area known to contain neuronal precursor cells. Colocalization of BrdU-immunolabeled cells with the neuron-specific markers turned on after division, 64 kDa, class III beta-tubulin, or microtubule-associated protein-2 showed that the vast majority of these mitotically active cells differentiated into neurons in the granule cell layer. Newly generated dentate granule cells also appeared in ectopic locations in the hilus and inner molecular layer of the dentate gyrus. Furthermore, developing granule cells projected axons aberrantly to both the CA3 pyramidal cell region and the dentate inner molecular layer. Induction of hippocampal seizure activity by perforant path stimulation resulted in an increase in SGZ mitotic activity similar to that seen with pilocarpine administration. These observations indicate that prolonged seizure discharges stimulate dentate granule cell neurogenesis, and that hippocampal network plasticity associated with epileptogenesis may arise from aberrant connections formed by newly born dentate granule cells.

View PDF Chat

Inflammatory Blockade Restores Adult Hippocampal Neurogenesis

2003-11-17

Michelle Monje , Hiroki Toda , Theo D. Palmer

Cranial radiation therapy causes a progressive decline in cognitive function that is linked to impaired neurogenesis. Chronic inflammation accompanies radiation injury, suggesting that inflammatory processes may contribute to neural stem … Cranial radiation therapy causes a progressive decline in cognitive function that is linked to impaired neurogenesis. Chronic inflammation accompanies radiation injury, suggesting that inflammatory processes may contribute to neural stem cell dysfunction. Here, we show that neuroinflammation alone inhibits neurogenesis and that inflammatory blockade with indomethacin, a common nonsteroidal anti-inflammatory drug, restores neurogenesis after endotoxin-induced inflammation and augments neurogenesis after cranial irradiation.

Identification of a Neural Stem Cell in the Adult Mammalian Central Nervous System

1999-01-01

Clas B. Johansson , Stefan Momma , Diana L. Clarke +3 more

View PDF Chat

Subventricular Zone Astrocytes Are Neural Stem Cells in the Adult Mammalian Brain

1999-06-01

Fiona Doetsch , Isabelle Caillé , Daniel A. Lim +2 more

View PDF Chat

Neuronal replacement from endogenous precursors in the adult brain after stroke

2002-08-05

Andreas Arvidsson , Tove Collin , Deniz Kirik +2 more

View PDF Chat

The Glial Nature of Embryonic and Adult Neural Stem Cells

2009-06-01

Arnold R. Kriegstein , Arturo Álvarez-Buylla

Glial cells were long considered end products of neural differentiation, specialized supportive cells with an origin very different from that of neurons. New studies have shown that some glial cells—radial … Glial cells were long considered end products of neural differentiation, specialized supportive cells with an origin very different from that of neurons. New studies have shown that some glial cells—radial glia (RG) in development and specific subpopulations of astrocytes in adult mammals—function as primary progenitors or neural stem cells (NSCs). This is a fundamental departure from classical views separating neuronal and glial lineages early in development. Direct visualization of the behavior of NSCs and lineage-tracing studies reveal how neuronal lineages emerge. In development and in the adult brain, many neurons and glial cells are not the direct progeny of NSCs, but instead originate from transit amplifying, or intermediate, progenitor cells (IPCs). Within NSCs and IPCs, genetic programs unfold for generating the extraordinary diversity of cell types in the central nervous system. The timing in development and location of NSCs, a property tightly linked to their neuroepithelial origin, appear to be the key determinants of the types of neurons generated. Identification of NSCs and IPCs is critical to understand brain development and adult neurogenesis and to develop new strategies for brain repair.

View PDF Chat

Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse

2015-12-16

Ye Zhang , Steven A. Sloan , Laura Clarke +7 more

View PDF Chat

Epigenetic Regulations of GABAergic Neurotransmission: Relevance for Neurological Disorders and Epigenetic Therapy

2016-03-23

Shikshya Shrestha , Steven M. Offer

Reelin, a large glycoprotein secreted by telencephalic GABAergic neurons, plays an important role in neuronal guidance embryonically and in synaptic plasticity postnatally. The reeler heterozygous mouse (+/rl) appears superficially normal … Reelin, a large glycoprotein secreted by telencephalic GABAergic neurons, plays an important role in neuronal guidance embryonically and in synaptic plasticity postnatally. The reeler heterozygous mouse (+/rl) appears superficially normal but has been of interest as an animal model for psychosis since the discovery that reelin is 50% down-regulated in postmortem psychotic brain. Brain abnormalities in +/rl are similar to psychotic brain and include a reduction in glutamic acid de carboxylase 67 (GAD67), dendritic arbors and spine density in cortex and hippocampus, and abnormalities in synaptic function including long-term potentiation (LTP). In spite of these abnormalities, behavioral abnormalities in +/rl are subtle and controversial. Recent findings indicate that the reelin (RELN) and GAD67 promoters are hypermethylated in GABAergic neurons of psychotic postmortem brain and that DNA methyltransferase 1 (DNMT1) is up-regulated. Hypermethlyation of RELN and GAD67 promoters can be induced by treating mice with methionine, and these mice display brain and behavioral abnormalities similar to +/rl. Thus, an animal model that combines genetic heterozygocity with epigenesis holds promise for understanding the role of Reelin down-regulation in psychosis.

View PDF Chat

High-Speed-Ventral-Plane Videography Identifies Specific Gait Pattern Changes in Cuprizone-Induced Demyelination in Mice

2025-06-24

Paula Giesler , Markus Kipp , Alexander Hawlitschka | Cells

Gait disturbances are among the most prominent motor symptoms in multiple sclerosis (MS), yet their functional characterization in preclinical models remains limited. In this study, we used high-speed ventral plane … Gait disturbances are among the most prominent motor symptoms in multiple sclerosis (MS), yet their functional characterization in preclinical models remains limited. In this study, we used high-speed ventral plane videography (DigiGait™) to analyze locomotor behavior during 5 weeks of cuprizone-induced demyelination in 10 male C57BL/6 mice. Gait analysis revealed significant alterations in stride time (left front paw from 0.303 ± 0.01 s to 0.257 ± 0.007 s; p = 0.003), paw angle (right fore paw from −13.78 ± 0.928° to 5.456 ± 2.146°; p = 0.003), and midline distance (right hind paw from 1.889 ± 0.099 cm to 1.216 ± 0.096 cm; p = 0.013), particularly in the hind limbs. These behavioral impairments correlated with histopathological findings of reduced myelination and elevated microglial activation in motor-relevant brain regions, including the corpus callosum, caudate-putamen, and motor cortex. Notably, specific gait parameters showed strong correlations with the degree of demyelination, supporting their relevance as functional biomarkers. Our data demonstrate that high-resolution gait analysis provides a sensitive, non-invasive tool to monitor functional deficits in demyelinating models and may aid in evaluating therapeutic efficacy in future studies.

Rnd3 deletion affects neuroblast behavior through the RhoA/ROCK pathway but not neural stem cells in postnatal mice subventricular zone

2025-06-23

Amalia Solana-Orts , Germán Belenguer , Begoña Ballester‐Lurbe +5 more | Frontiers in Cell and Developmental Biology

In the subventricular zone (SVZ), neural stem cells (NSCs) generate neural progenitor cells (NPCs), which proliferate and differentiate into neuroblasts (NBs) that will travel along the rostral migratory stream (RMS) … In the subventricular zone (SVZ), neural stem cells (NSCs) generate neural progenitor cells (NPCs), which proliferate and differentiate into neuroblasts (NBs) that will travel along the rostral migratory stream (RMS) to the olfactory bulbs (OBs), where they mature into interneurons. Rnd3, a member of the Rho GTPase family, regulates cytoskeletal dynamics, neuronal morphology, and survival, primarily by interacting with the RhoA/ROCK pathway. In the central nervous system, Rnd3 is highly expressed during early postnatal development and is essential for neural function, axonal myelination, and neuronal polarization, as its deficiency leads to severe motor and neurodevelopmental impairments. In this study we show that NBs from Rnd3 KO mice accumulate in the SVZ and that these are principally characterized as late/migrating NBs. We investigated whether the observed accumulation results from increased proliferation and/or differentiation potential of NSCs and NPCs, and/or altered NB migration to the OBs through the RMS, potentially accompanied by increased proliferation. Our in vitro experiments indicate that the loss of Rnd3 does not affect NSC behavior. In addition, RNA sequencing reveals that Rnd3 expression is highest in NBs, particularly in late-stage NBs, suggesting a potential role in migration. Furthermore, gene expression analyses indicate that the loss of Rnd3 may disrupt NB cytoskeletal dynamics by altering the expression of key components of the RhoA/ROCK signaling pathway. These findings provide mechanistic insights into how Rnd3 deletion impairs NB migration.

Neocortical neurogenesis: a proneural gene perspective

2025-06-22

Lakshmy Vasan , Alexandra Moffat , Pierre Mattar +1 more | FEBS Journal

The neocortex, which is the site of higher‐order cognitive functioning, is comprised of two main neuronal types: excitatory (E) and inhibitory (I). Neurodevelopmental disorders that disrupt the balance of E:I … The neocortex, which is the site of higher‐order cognitive functioning, is comprised of two main neuronal types: excitatory (E) and inhibitory (I). Neurodevelopmental disorders that disrupt the balance of E:I neurotransmission predispose individuals to atypical brain function, highlighting the importance of generating the correct numbers of each neuronal type. During development, neurons with E and I neurotransmission profiles are primarily generated from neural stem and progenitor cells (NPCs), located in the dorsal and ventral telencephalon, respectively. To ensure that correct numbers of each neuronal type are generated, NPC differentiation dynamics vary depending on positional and temporal information and host species. Despite variations in NPC differentiation kinetics and outcomes, proneural genes encoding basic helix–loop–helix (bHLH) transcription factors (TFs) have remained constant as the core drivers of neurogenesis and neuronal subtype specification from fly to human. This high degree of functional conservation raises the question of how proneural TF activity is regulated to control precise neurogenic patterns. In the neocortex, the proneural genes neurogenin 1 ( Neurog1 ) and Neurog2 specify an excitatory neuronal identity in dorsal telencephalic NPCs, whereas achaete–scute family bHLH transcription factor 1 ( Ascl1 ) specifies an inhibitory neurotransmission fate in ventral NPCs, generating interneurons that then migrate tangentially to enter the neocortex. Here, we review our current knowledge of how Neurog1/Neurog2 and Ascl1 functions are regulated to ensure that E:I balance is ultimately achieved in the lissencephalic murine cortex and in gyrencephalic species. Together, these studies point to emergent and conserved features of proneural gene regulation and function across evolutionary time.

Twinfilin-1 phosphorylation in reelin signaling regulates actin dynamics and spine development

2025-06-21

Geyao Dong , Daisuke Mori , Tetsuo Matsuzaki +7 more | bioRxiv (Cold Spring Harbor Laboratory)

Reelin is an extracellular glycoprotein essential for neuronal migration, spine development, and synaptic plasticity. Impaired reelin signaling is linked to neurological disorders, including schizophrenia and autism. While reelin mutant (reeler) … Reelin is an extracellular glycoprotein essential for neuronal migration, spine development, and synaptic plasticity. Impaired reelin signaling is linked to neurological disorders, including schizophrenia and autism. While reelin mutant (reeler) mice exhibit behavioral deficits associated with impaired spine formation, the underlying molecular mechanisms remain unclear. We identified Twinfilin-1 (Twf1) as a downstream effector of reelin signaling via phosphoproteomic analysis, based on its reduced tyrosine phosphorylation in reeler mice. We found that Src regulated Twf1 phosphorylation at tyrosine 309, and reelin stimulation increased Twf1 phosphorylation in neurons, an effect blocked by the Src inhibitor PP2. A phospho-resistant Twf1 mutant (Twf1 Y309F) showed reduced capping protein binding and a lower F/G-actin ratio. Twf1Y309F mice exhibited cognitive deficits, reduced spine density, smaller spine head size, and a decreased F/G-actin ratio in synaptosomes. These findings highlight Twf1 phosphorylation as a key component of reelin signaling involved in actin remodeling and spine development.

PGC-1α Expands Neural Precursor Pool and Facilitates Cognitive Recovery Within AD Hippocampus Through the Regulation of Mitochondrial Dynamics

2025-06-20

Yuxin Wang , Yijie Wang , Wen Pan +7 more | Molecular Neurobiology

Neural stem cells in adult neurogenesis and their therapeutic applications in neurodegenerative disorders: a concise review

2025-06-19

Teketay Bayleyegn Derso , Bemrew Admassu Mengistu , Yitayew Demessie +2 more | Frontiers in Molecular Medicine

The idea of using stem cell therapy to treat neurodegenerative diseases has undergone significant change over the years and has made significant progress recently. Neurotrophins, growth factors, and transcription factors … The idea of using stem cell therapy to treat neurodegenerative diseases has undergone significant change over the years and has made significant progress recently. Neurotrophins, growth factors, and transcription factors regulate neural stem cell proliferation and differentiation. Disruption of these regulatory mechanisms, including negative feedback, can contribute to neurodegenerative diseases. Contemporary research highlights a growing global concern regarding diverse neurodegenerative disorders affecting both humans and animals. These conditions arise from neuronal cell death, axonal regeneration failure, and impairment of neuronal structure. Current pharmacological treatments primarily offer symptomatic relief without altering disease progression. Consequently, researchers are investigating innovative therapeutic strategies, with neural stem cell therapy emerging as a promising avenue. Adult neural stem cells, embryonic neural stem cells, and induced pluripotent stem cells represent potential cell sources, although challenges such as ethical considerations and technical limitations remain. The therapeutic application of neural stem cells holds significant promise for addressing neurodegenerative diseases, including Alzheimer’s disease, stroke, amyotrophic lateral sclerosis, spinal cord injury, and multiple sclerosis. Neural stem cell therapy aims to replenish lost neurons and promote neural regeneration in these conditions. While clinical trials have demonstrated some success in improving cognitive and motor functions in individuals with neurodegenerative impairments, challenges such as immunological rejection, the identification of compatible cell sources, ethical concerns, treatment efficacy, and potential side effects necessitate thorough investigation before widespread clinical implementation. Despite these challenges, neural stem cell-based therapy offers substantial potential for revolutionizing the treatment of neurodegenerative diseases and central nervous system injuries. This paper, therefore, explores adult neurogenesis and the therapeutic potential of neural stem cells within the dynamic field of neurodegenerative disorders.

Role of Brain-Derived Neurotrophic Factor Expression Through Microglial Polarization in Adult Hippocampal Neurogenesis with Major Depressive Disorder

2025-06-19

Meihua Lu | Theoretical and Natural Science

In 2021, an estimation of 14.5 million U.S. adults had experienced Major Depressive Disorder (MDD). Among them, nearly 40% of the population doesnt receive treatment. MDD is characterized by cognitive … In 2021, an estimation of 14.5 million U.S. adults had experienced Major Depressive Disorder (MDD). Among them, nearly 40% of the population doesnt receive treatment. MDD is characterized by cognitive deficits and impaired neurogenesis. Recent studies have identified Brain-Derived Neurotrophic Factor (BDNF) to be a crucial player in neuroplasticity and neurogenesis, with question remaining regarding its complex correlation with microglial cells and -site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE-1) Inhibitors. This paper reviews the interplay between BDNF expression, microglial polarization, and adult hippocampal neurogenesis in the context of MDD, highlighting potential therapeutic implications.

The Role of Adult Hippocampal Neurogenesis in Alzheimer's Disease: Mechanisms, Therapeutic Potential, and Future Directions

2025-06-19

H. J. Yang | Theoretical and Natural Science

Alzheimers disease (AD) is characterized by progressive cognitive deterioration. Besides the pathological features of amyloid-beta plaques and tau tangles, emerging research implicates impaired adult hippocampal neurogenesis (AHN) in the dentate … Alzheimers disease (AD) is characterized by progressive cognitive deterioration. Besides the pathological features of amyloid-beta plaques and tau tangles, emerging research implicates impaired adult hippocampal neurogenesis (AHN) in the dentate gyrus as a contributing factor. Impaired AHN in AD is marked by reduced neural stem cells activation, diminished progenitor cell proliferation, and abnormal neuronal maturation. This review explores the role of AHN in AD, delves into the disrupted molecular mechanisms underlying AHN dysfunction in AD, while assesses potential therapeutic strategies aimed at restoring neurogenesis to treat AD. Understanding AHNs role in AD could inform future diagnostic and therapeutic approaches.

Adeno-associated virus-mediated inhibition of ROCK2 promotes synaptogenesis and neurogenesis in rats after ischemic stroke

2025-06-19

Liuliu Shi , Ting Zhu , Chengyan Ge +3 more | Neural Regeneration Research

Abstract Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke. Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity, resulting in … Abstract Neurite outgrowth and synaptogenesis are critical steps for functional recovery following ischemic stroke. Damaged axons of the central nervous system in adult mammals exhibit limited regenerative capacity, resulting in enduring neurological deficits. Recent findings from our research indicate that inhibition of Rhoassociated kinase (ROCK)2 facilitates neuroprotection in different models of central nervous system diseases. In addition, our prior studies have demonstrated that axonal protection enhances the regeneration of injured axons. However, it remains unclear whether the axonal protection mediated by ROCK2 inhibition also facilitates synaptogenesis. In this study, we aimed to investigate the effects of inhibiting ROCK2 expression on synaptogenesis and neurogenesis in ischemic stroke using an shRNA-expressing adeno-associated virus (AAV) vector (AAV-sh.ROCK2). We demonstrated that AAV-sh.ROCK2 increased neurite outgrowth and facilitated synaptogenesis in vivo . Furthermore, AAV-sh.ROCK2 increased neuronal survival and promoted neurogenesis following middle cerebral artery occlusion surgery as well as long-term motor functional recovery after ischemia/reperfusion injury. Notably, AAV-sh.ROCK2 also stimulated serotonergic and dopaminergic axon sprouting after ischemia/reperfusion injury. Mechanistically, AAV-sh.ROCK2 activity resulted in increased anti-collapsin response mediator protein 2 activation and reductions in RhoA and ROCK2 expression. Our study identified ROCK2 as a critical regulator of synaptogenesis and neurogenesis, highlighting it as a promising target to facilitate neuroprotection and regeneration in ischemic stroke.

Choline transporters are required for oligodendrocyte differentiation and myelin sheath formation in mouse postnatal brain

2025-06-19

Mingchen Liu , Bin Yu , Yu Xia +7 more | Cell Reports

The extracellular matrix glycoprotein tenascin-C supports the enriched environment-stimulated neurogenesis in the adult dentate gyrus of mice

2025-06-18

Milena Korenić , Andrej Korenić , Vera Stamenković +2 more | Biochemical and Biophysical Research Communications

Protective impact of physical exercise on methamphetamine-induced neuroinflammation and neurogenesis impairment depends on the activity level

2025-06-17

Mateusz Smolarz , Magdalena Dębiec , Gracjana Zając +7 more | Brain Behavior and Immunity

Restoration of Mitochondrial Homeostasis by Wnt3a/β-catenin/c-Myc Alleviates Cadmium-Induced Neural Stem Cell Senescence and Cognitive Impairment in Mouse Hippocampus

2025-06-17

Yuwei Zhang , Qiuyun Gu , Yixi Li +7 more | Journal of Hazardous Materials

Start the Engine of Neuroregeneration: A Mechanistic and Strategic Overview of Direct Astrocyte-to-Neuron Reprogramming

2025-06-17

H. Jiang , H. R. Qi , Anying Tang +2 more | Ageing Research Reviews

Characterization of adult hippocampal neurogenesis in adult and aged genetically diverse mice

2025-06-17

Andrea Finch , Alexander McNamara , Kristen D. Onos +3 more | GeroScience

Abstract Adult hippocampal neurogenesis—the generation of new neurons in the adult brain—declines with age, contributing to cognitive deficits in aging. While the majority of mammalian studies on neurogenesis have utilized … Abstract Adult hippocampal neurogenesis—the generation of new neurons in the adult brain—declines with age, contributing to cognitive deficits in aging. While the majority of mammalian studies on neurogenesis have utilized inbred mouse strains, these models do not fully capture the genetic diversity of humans, limiting the translational relevance of their findings. The Diversity Outbred (DO) mouse model, a genetically heterogeneous population, provides a promising alternative to traditional inbred strains. In this study, we investigated how genetic diversity influences hippocampal neurogenesis by comparing neurogenesis in adult and aged Diversity Outbred (DO) mice with the commonly used C57BL/6J inbred strain. While both strains exhibited a decline in neurogenesis with age, DO mice showed significantly lower levels of neurogenesis compared to C57BL/6J mice, even in young adults. Additionally, we observed that the wild-derived CAST/EiJ strain, one of the eight founder strains in the DO model, contributed to this reduction in neurogenesis. Our findings highlight the importance of genetic diversity in neurogenesis research and suggest that the DO model may better represent human genetic diversity associated with age-related decline in neurogenesis.

Pnky Modulates Neural Stem Cell Proliferation and Differentiation Through Activation of Wnt/β-Catenin Signaling Pathway

2025-06-16

Haidong Wu , Jing Huang , Xiaojing Li +3 more | Organogenesis

Neural stem cell (NSC) possess the essential properties of pluripotency and self-renewal, making them promising candidates for the treatment of neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), … Neural stem cell (NSC) possess the essential properties of pluripotency and self-renewal, making them promising candidates for the treatment of neurological disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and spinal cord injuries. While previous studies have identified the long non-coding RNAs (lncRNAs) Pnky as a regulator of NSC differentiation into neurons via RNA splicing, its role in NSC differentiation and proliferation through the Wnt/β-catenin pathway remains unclear. In this study, we investigated the mechanism by which Pnky influences the Wnt/β-catenin pathway to promote NSC differentiation into neurons. Using cck8 assays, western blot analysis, and quantitative polymerase chain reaction (qPCR), we found that Pnky knockdown significantly enhanced NSC proliferation and promoted their differentiation into neurons. Additionally, Pnky knockdown resulted in the downregulation of the neural stem cell marker Nestin and upregulation of the neuronal marker β3-Tubulin, through activation of the β-catenin signaling pathway. Conversely, inhibiting the β-catenin pathway hindered both NSC differentiation and proliferation. These findings suggest that targeting the Pnky-mediated Wnt/β-catenin pathway may offer novel strategies for the treatment, diagnosis, and drug development of central nervous system diseases.

Epigenetic Reprogramming of Cell Identity in the Rat Primary Neuron–Glia Cultures Involves Histone Serotonylation

2025-06-15

А. А. Бородинова , Yulia A. Leontovich , Alexander Beletskiy +3 more | Cells

Epigenetic rearrangements can create a favorable environment for the intrinsic plasticity of brain cells, leading to cellular reprogramming into virtually any cell type through the induction of cell-specific transcriptional programs. … Epigenetic rearrangements can create a favorable environment for the intrinsic plasticity of brain cells, leading to cellular reprogramming into virtually any cell type through the induction of cell-specific transcriptional programs. In this study, we assessed how chromatin remodeling induced by broad-spectrum HDAC inhibitors affects cellular differentiation trajectories in rat primary neuron-glia cultures using a combination of transcriptomics, qPCR, and cytochemistry. We described the epigenetic regulation of transcriptional programs controlled by master transcription factors and neurotrophins in the context of neuronal and glial differentiation and evaluated the expression of representative cell-specific markers. The results obtained suggest that HDAC inhibitors reduce the proliferative potential of cultured cells and induce transcriptomic changes associated with cell differentiation and specialization. Particularly, we revealed a significant upregulation of genes typically expressed in neuromodulatory neurons and the downregulation of genes expressed in glia and inhibitory neurons. Transcriptional changes were accompanied by continuous elevation of histone serotonylation levels in both neurons and glia. Emerging shortly after HDAC inhibition, a complex chromatin remodeling, which includes histone serotonylation, persists over many hours in distinct brain cells. We assume that this sustained epigenetic mechanism likely helps to maintain transcriptional changes associated with cell fate commitment, possibly priming cells for long-term fate conversion.

Myelin dysfunction in aging and brain disorders: mechanisms and therapeutic opportunities

2025-06-15

Zhihai Huang , Yulan Zhang , Peibin Zou +2 more | Molecular Neurodegeneration

Abstract Myelin is a multilamellar membrane that surrounds axons in the vertebrate nervous system. Properly functioning myelin is essential for the rapid conduction of nerve impulses, and it metabolically supports … Abstract Myelin is a multilamellar membrane that surrounds axons in the vertebrate nervous system. Properly functioning myelin is essential for the rapid conduction of nerve impulses, and it metabolically supports axonal integrity. Emerging evidence indicates that myelin is also involved in various aspects of cognition, with adaptive myelination playing a critical role in memory consolidation and motor learning. However, these physiological processes can be disrupted in various diseases. Understanding the mechanisms underlying myelin pathology is therefore essential for the development of targeted therapies for associated medical conditions. This review provides a comprehensive overview of the role of myelin in neural function, with a particular focus on adaptive myelination in cognition. We also highlight myelin dysfunction and the underlying mechanisms in the aging brain, as well as in diverse brain disorders and neurological conditions, including neurodegenerative diseases, psychiatric conditions, brain injuries, chemotherapy-related cognitive impairment, and neurological symptoms associated with COVID-19. Furthermore, we discuss the therapeutic potential of recently identified pro-myelinating compounds in aging-associated cognitive decline and brain disorders, as well as the future of remyelination therapies. Current evidence suggests that restoring functional myelin may serve as a therapeutic strategy for various medical conditions associated with myelin dysfunction.

CACNA1A loss-of-function affects neurogenesis in human iPSC-derived neural models

2025-06-14

Ilaria Musante , Davide Cangelosi , Lorenzo Muzzi +7 more | Cellular and Molecular Life Sciences

Abstract CACNA1A encodes the pore-forming α 1A subunit of the Ca V 2.1 calcium channel, whose altered function is associated with various neurological disorders, including forms of ataxia, epilepsy, and … Abstract CACNA1A encodes the pore-forming α 1A subunit of the Ca V 2.1 calcium channel, whose altered function is associated with various neurological disorders, including forms of ataxia, epilepsy, and migraine. In this study, we generated isogenic iPSC-derived neural cultures carrying CACNA1A loss-of-function mutations differently affecting Ca V 2.1 splice isoforms. Morphological, molecular, and functional analyses revealed an essential role of CACNA1A in neurodevelopmental processes. We found that different CACNA1A loss-of-function mutations produce distinct neurodevelopmental deficits. The F1491S mutation, which is located in a constitutive domain of the channel and therefore causes a complete loss-of-function, impaired neural induction at very early stages, as demonstrated by changes in single-cell transcriptomic signatures of neural progenitors, and by defective polarization of neurons. By contrast, cells carrying the Y1854X mutation, which selectively impacts the synaptically-expressed Ca V 2.1[EFa] isoform, behaved normally in terms of neural induction but showed altered neuronal network composition and lack of synchronized activity. Our findings reveal previously unrecognized roles of CACNA1A in the mechanisms underlying neural induction and neural network dynamics and highlight the differential contribution of the divergent variants Ca V 2.1[EFa] and Ca V 2.1[EFb] in the development of human neuronal cells.

Beyond the hippocampus: Limbic white matter injury implicated in post-radiation memory performance in primary brain tumor patients

2025-06-13

Alexander S. Qian , Roshan Karunamuni , Soumya Unnikrishnan +7 more | Neuro-Oncology

Abstract Background Limbic white matter (WM) of the Papez circuit, including the fornix, dorsal cingulum, and parahippocampal cingulum (PHC), interplay with the hippocampus as key components of the memory network. … Abstract Background Limbic white matter (WM) of the Papez circuit, including the fornix, dorsal cingulum, and parahippocampal cingulum (PHC), interplay with the hippocampus as key components of the memory network. We analyzed biomarkers of injury to these pathways to understand their impact on post-radiation therapy (RT) memory performance. Methods Primary brain tumor patients on a prospective trial receiving fractionated brain RT (n=57) underwent volumetric MRI, diffusion tensor imaging, and memory assessments (Hopkins Verbal Learning Test-Revised [HVLT-R] Total and Delayed Recall and Brief Visuospatial Memory Test -Revised [BVMT-R] Total and Delayed Recall) at baseline and 3, 6, and 12 months post-RT. MRI biomarkers included volume, fractional anisotropy (FA), and mean diffusivity (MD). Linear mixed-effects models assessed associations between biomarkers and memory performance over time. Results Smaller volumes in the right fornix was associated with lower BVMT-R-Total scores (p=0.019) and left PHC volume loss was associated with worse performance on BVMT-R-Delayed (p=0.039). Lower FA in the left (p=0.010) and right (p=0.019) fornix was associated with lower BVMT-R-Total performance. Lower FA in the left dorsal cingulum (p=0.038) and right PHC (p=0.039) were associated with lower HVLT-R-Total and HVLT-R-Delayed scores, respectively. Higher MD in bilateral fornix (p=0.01) and right PHC (p=0.011) correlated with lower BVMT-R-Total scores; higher MD in the right PHC (p=0.046) also correlated with lower HVLT-R-Total scores. Hippocampal volume was not associated with memory scores. Conclusion Poorer microstructural integrity in limbic WM tracts of the Papez circuit predicted worse memory performance, while hippocampal injury did not. Dose avoidance in these tracts may preserve memory outcomes.

Chronic α5‐<scp>GABA</scp>‐A Receptor Potentiation Promotes Mouse Adult Hippocampal Neurogenesis

2025-06-13

Thomas D. Prévot , Michael Marcotte , Denis J. David +5 more | Hippocampus

Several lines of evidence implicate adult hippocampal neurogenesis (AHN) in cognitive functions, in mood- and anxiety-related behaviors, and in the therapeutic effects of antidepressants. Augmenting α5-γ-Aminobutyric acid type A (GABAA) … Several lines of evidence implicate adult hippocampal neurogenesis (AHN) in cognitive functions, in mood- and anxiety-related behaviors, and in the therapeutic effects of antidepressants. Augmenting α5-γ-Aminobutyric acid type A (GABAA) receptor function has shown neurotrophic effects in stress and aged models, but its impact on mouse AHN remains unknown. Adult male 129S6/SvEvTac mice (n = 30 total) were treated for 6 weeks with GL-II-73, an α5-GABAA-R-positive allosteric modulator (α5-PAM) [30 mg/kg, per os, (P.O.)] or fluoxetine, a prototypical selective serotonin reuptake inhibitor known to increase AHN (18 mg/kg, P.O.). Proliferation in the subgranular zone of the dentate gyrus (DG) was assessed by the level of Ki67, a marker of dividing cells; survival of the young neurons was assessed by retention of the 5-Bromo-2´-Deoxyuridine (BrdU) nucleotide analog injected 2 weeks before sacrifice. Finally, maturation of young adult-born neurons was evaluated by measuring the fraction of BrdU-positive cells that are also DCX and/or NeuN-positive, capturing overall maturation and speed of maturation. Similarly to fluoxetine, a chronic treatment with GL-II-73 stimulated all stages of AHN, significantly increasing neuronal progenitor proliferation, survival of adult-born granule cells, and maturation of young neurons in the DG of the hippocampus. Chronic treatment with GL-II-73, a α5-GABAA-R-positive allosteric modulator, increased AHN, including cellular proliferation, survival, and maturation of newborn neurons, to levels comparable to fluoxetine.

Exploration of Cytokines That Impact the Therapeutic Efficacy of Mesenchymal Stem Cells in Alzheimer’s Disease

2025-06-12

Herui Wang , Chonglin Zhong , Yi Mi +6 more | Bioengineering

Current therapies for Alzheimer’s disease (AD) includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and amyloid beta (Aβ)/Tau-targeting drugs. While these drugs improve cognitive decline and target the pathological mechanisms, their outcomes … Current therapies for Alzheimer’s disease (AD) includes acetylcholinesterase inhibitors, NMDA receptor antagonists, and amyloid beta (Aβ)/Tau-targeting drugs. While these drugs improve cognitive decline and target the pathological mechanisms, their outcomes still are still in debate. Mesenchymal stem cells (MSCs) offer a regenerative approach by modulating neuroinflammation and promoting neuroprotection. Although the paracrine of MSCs is efficient in various AD preclinical studies and the exosomes of MSCs have entered clinical trials, the key cytokines driving the efficacy remain unclear. Here, we evaluated human umbilical cord-derived MSCs (hUC-MSCs) and employed gene-silenced MSCs (siHGF-MSCs, siTNFR1-MSCs, siBDNF-MSCs) in APP/PS1 AD mice to investigate specific mechanisms. hUC-MSCs significantly reduced Aβ/Tau pathology and neuroinflammation, with cytokine-specific contributions: silencing HGF predominantly reduced Aβ/Tau clearance, although silencing TNFR1 or BDNF showed modest effects; silencing TNFR1 or BDNF more prominently weakened anti-neuroinflammation, while silencing HGF exerted a weaker influence. All three cytokines partially contributed to oxidative stress reduction and cognitive improvements. Our study highlights MSC-driven AD alleviation as a multifactorial strategy and reveals specific cytokines alleviating different aspects of AD pathology.

Reelin-LRP8 signaling mediates brain dissemination of breast cancer cells via abluminal migration

2025-06-12

Haofeng Huang , Min Zhang , Enyu Huang +7 more | EMBO Molecular Medicine

A mathematical model suggests collectivity and inconstancy enhance the efficiency of neuronal migration in the adult brain

2025-06-05

Daiki Wakita , Yuriko Sobu , Naoko Kaneko +1 more | PLoS Computational Biology

Neuronal regeneration in the adult brain, which is restricted compared to that in the embryonic brain, is a long-standing topic in neuroscience and medical research. Based on studies in mammals, … Neuronal regeneration in the adult brain, which is restricted compared to that in the embryonic brain, is a long-standing topic in neuroscience and medical research. Based on studies in mammals, a small number of newly generated immature neurons (neuroblasts) migrate toward damaged sites and contribute to functional recovery. During migration, neuroblasts form chain-like collectives and modify the morphology of glial cells (astrocytes), which are the main components of the surrounding environment. However, it remains unclear how neuroblasts form collectives and how efficient migration is achieved through collective formation in a pool of astrocytes. The main difficulty lies in tracking individual neuroblasts within the collective, both in vitro and in vivo, over a period. To address this impasse, we built a mathematical model of the neuroblast-astrocyte system to assess its long-term performance in silico. Our simulations showed that individual neuroblasts gathered into chain-like collectives through occasional contact, astrocyte confinement, and moderate adhesion between the neuroblasts. The forward movement of neuroblasts in an astrocyte-dense environment was accelerated if we assumed a simple interaction: the higher the number of neuroblasts near an astrocyte, the stronger the shrinkage of astrocytic protrusions. Furthermore, temporal changes in neuroblast behavior, as indicated by our observation of living neuroblasts in culture, reinforce the advantages of simulated collectives. A collective of neuroblasts with constant behavior sometimes repeated non-migratory movements, whereas those with inconstant behavior were easily untangled, resulting in a rapid migration. These results highlight the potential for neuroblast collectivity and inconstancy in enhancing neuronal regeneration in the adult brain.

Epigenetic regulation of neural stem cell aging in the mouse hippocampus by Setd8 downregulation

2025-06-03

Shuzo Matsubara , Kanae Matsuda‐Ito , Haruka Sekiryu +6 more | The EMBO Journal

Neural stem cells (NSCs) in the mammalian brain decline rapidly with age, leading to impairment of hippocampal memory function in later life. However, the relationship between epigenetic remodeling and transcriptional … Neural stem cells (NSCs) in the mammalian brain decline rapidly with age, leading to impairment of hippocampal memory function in later life. However, the relationship between epigenetic remodeling and transcriptional regulation that compromises hippocampal NSC activity during the early stage of chronological aging remains unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on NSCs and newly generated neurons across different stages. Integrated data analysis revealed continuous alterations in the chromatin profile of hippocampal NSCs and their progeny from neonatal to mature adult stages, accompanied by consistent changes in transcriptional profiles. Further, decreased expression of Setd8, encoding the enzyme for histone H4 monomethylation at lysine 20 (H4K20me1), underlies age-related changes in mouse hippocampal NSCs. Notably, depletion of Setd8 elicits alterations in gene expression and epigenetic regulation that phenocopy age-related changes, and impairs NSC activity, leading to hippocampal memory deficits. Together, our study provides a global map of longitudinal chromatin and transcriptome changes during brain aging and identifies mechanistic insights into early-onset decline of NSC activity and hippocampal neurogenesis that precedes functional aging.

Loss of <scp>NFIA</scp> Impairs Adult Hippocampal Neurogenesis

2025-06-03

Mi Wang , Rebekah van Bruggen , Lanah Mohammed +2 more | Hippocampus

ABSTRACT Adult hippocampal neurogenesis (AHN) is the process by which new neurons are continuously generated from neural stem and progenitor cells (NSPCs) in the adult dentate gyrus. AHN plays a … ABSTRACT Adult hippocampal neurogenesis (AHN) is the process by which new neurons are continuously generated from neural stem and progenitor cells (NSPCs) in the adult dentate gyrus. AHN plays a pivotal role in cognitive functions, including learning, memory, and mood regulation. Transcription factors regulate AHN by maintaining the NSPC pool and facilitating lineage progression. The nuclear factor I (NFI) transcription factor family member NFIA is critical for neurogenesis and gliogenesis during early brain development, but its role in adult neurogenesis remains poorly understood. Here, we generated an inducible Nfia loss‐of‐function mouse model to investigate the role of NFIA in Ascl1‐ lineage adult‐born neurons. By tracking lineage progression from NSPCs to mature neurons, we found that NFIA deletion significantly reduced neurogenesis. Populations of NSPCs, neuroblasts, and mature granule neurons were all similarly diminished, indicating a primary defect in NSPC maintenance. Behaviorally, NFIA loss impaired hippocampal‐dependent contextual fear memory without affecting locomotor activity, anxiety levels, spatial memory, or cued fear memory. Our findings demonstrate that NFIA is crucial for AHN and hippocampus‐dependent contextual memory, thereby providing insights into its role in adult neurogenesis.

Forebrain neural progenitors effectively integrate into host brain circuits and improve neural function after ischemic stroke

2025-06-03

Xiao He , Jiadong Chen , Yan Zhong +7 more | Nature Communications

Human cortical neural progenitor cell transplantation holds significant potential in cortical stroke treatment by replacing lost cortical neurons and repairing damaged brain circuits. However, commonly utilized human cortical neural progenitors … Human cortical neural progenitor cell transplantation holds significant potential in cortical stroke treatment by replacing lost cortical neurons and repairing damaged brain circuits. However, commonly utilized human cortical neural progenitors are limited in yield a substantial proportion of diverse cortical neurons and require an extended period to achieve functional maturation and synaptic integration, thereby potentially diminishing the optimal therapeutic benefits of cell transplantation for cortical stroke. Here, we generated forkhead box G1 (FOXG1)-positive forebrain progenitors from human inducible pluripotent stem cells, which can differentiate into diverse and balanced cortical neurons including upper- and deep-layer excitatory and inhibitory neurons, achieving early functional maturation simultaneously in vitro. Furthermore, these FOXG1 forebrain progenitor cells demonstrate robust cortical neuronal differentiation, rapid functional maturation and efficient synaptic integration after transplantation into the sensory cortex of stroke-injured adult rats. Notably, we have successfully utilized the non-invasive 18F-SynVesT-1 PET imaging technique to assess alterations in synapse count before and after transplantation therapy of FOXG1 progenitors in vivo. Moreover, the transplanted FOXG1 progenitors improve sensory and motor function recovery following stroke. These findings provide systematic and compelling evidence for the suitability of these FOXG1 progenitors for neuronal replacement in ischemic cortical stroke.