Development Of Dentate Gyrus Research Articles

Intermediate progenitors support migration of neural stem cells into dentate gyrus outer neurogenic niches.

The hippocampal dentate gyrus (DG) is a unique brain region maintaining neural stem cells (NCSs) and neurogenesis into adulthood. We used multiphoton imaging to visualize genetically defined progenitor subpopulations in live slices across key stages of mouse DG development, testing decades old static models of DG formation with molecular identification, genetic-lineage tracing, and mutant analyses. We found novel progenitor migrations, timings, dynamic cell-cell interactions, signaling activities, and routes underlie mosaic DG formation. Intermediate progenitors (IPs, Tbr2+) pioneered migrations, supporting and guiding later emigrating NSCs (Sox9+) through multiple transient zones prior to converging at the nascent outer adult niche in a dynamic settling process, generating all prenatal and postnatal granule neurons in defined spatiotemporal order. IPs (Dll1+) extensively targeted contacts to mitotic NSCs (Notch active), revealing a substrate for cell-cell contact support during migrations, a developmental feature maintained in adults. Mouse DG formation shares conserved features of human neocortical expansion.

Apolipoprotein E regulates the maturation of injury-induced adult-born hippocampal neurons following traumatic brain injury.

Various brain injuries lead to the activation of adult neural stem/progenitor cells in the mammalian hippocampus. Subsequent injury-induced neurogenesis appears to be essential for at least some aspects of the innate recovery in cognitive function observed following traumatic brain injury (TBI). It has previously been established that Apolipoprotein E (ApoE) plays a regulatory role in adult hippocampal neurogenesis, which is of particular interest as the presence of the human ApoE isoform ApoE4 leads to significant risk for the development of late-onset Alzheimer's disease, where impaired neurogenesis has been linked with disease progression. Moreover, genetically modified mice lacking ApoE or expressing the ApoE4 human isoform have been shown to impair adult hippocampal neurogenesis under normal conditions. Here, we investigate how controlled cortical impact (CCI) injury affects dentate gyrus development using hippocampal stereotactic injections of GFP-expressing retroviruses in wild-type (WT), ApoE-deficient and humanized (ApoE3 and ApoE4) mice. Infected adult-born hippocampal neurons were morphologically analyzed once fully mature, revealing significant attenuation of dendritic complexity and spine density in mice lacking ApoE or expressing the human ApoE4 allele, which may help inform how ApoE influences neurological diseases where neurogenesis is defective.

Transcription Factor 4 Safeguards Hippocampal Dentate Gyrus Development by Regulating Neural Progenitor Migration.

The dentate gyrus (DG) of the hippocampal formation plays essential roles in learning and memory. Defective DG development is associated with neurological disorders. Here, we show that transcription factor 4 (Tcf4) is essential for DG development. Tcf4 expression is elevated in neural progenitors of the dentate neuroepithelium in the developing mouse brain. We demonstrate that conditional disruption of Tcf4 in the dentate neuroepithelium leads to abnormal neural progenitor migration guided by disorganized radial glial fibers, which further leads to hypoplasia in the DG. Moreover, we reveal that Wnt7b is a key downstream effector of Tcf4 in regulating neural progenitor migration. Behavioral analysis shows that disruption of integrity of the DG impairs the social memory highlighting the importance of proper development of the DG. These results reveal a critical role for Tcf4 in regulating DG development. As mutations in TCF4 cause Pitt-Hopkins syndrome (PTHS) characterized by severe intellectual disability, our data also potentially provide insights into the basis of neurological defects linked to TCF4 mutations.

Maternal exposure to swainsonine impaired the early postnatal development of mouse dentate gyrus of offspring

Neurogenesis in the dentate gyrus (DG) plays a key role in the normal of structure and function of the hippocampus—learning and memory. After eating the locoweeds, animals develop a chronic neurological disease called “locoism”. Swainsonine (SW) is the main toxin in locoweeds. Studies have shown that SW induces neuronal apoptosis in vitro and impairs learning and memory in adult mouse. The present study explored effects of SW exposure to dams on the postnatal neurogenesis of DG of offspring. Pregnant ICR mice were orally gavaged with SW at a dose of 0, 5.6 or 8.4 mg/kg/day from gestation day 10 to postnatal day (PND) 21, respectively. We found that SW impaired the proliferation capacity of neural progenitor cells in the DG so that the number of newborn cells was reduced at PND 8. Using the postnatal in vivo electroporation, we showed that the dendritic branching and total length of granule cells were significantly decreased due to SW exposure. In addition, on PND 21, the density of NeuN-positive and Reelin-positive interneurons increased in the hilus, implying the disorder of neuronal migration. These results suggest that maternal exposure to SW, the neurogenesis of DG on offspring was disrupted, finally leading to the functional disorder of DG.

Defining the Vulnerability Window of Anesthesia-Induced Neuroapoptosis in Developing Dentate Gyrus Granule Cells — A Transgenic Approach Utilizing POMC-EGFP Mice

Exposure to commonly used anesthetics is associated with widespread neuroapoptosis in neonatal animals. Vulnerability of developing hippocampal dentate gyrus granule cells to anesthetic neurotoxicity peaks approximately 2 weeks after cell birth, as measured by bromodeoxyuridine birth dating, regardless of the age of the animal. The present study examined whether the vulnerable window can be further characterized by utilizing a transgenic approach. Proopiomelanocortin enhanced green fluorescent protein (POMC-EGFP) mice (postnatal day 21) were exposed to 3% sevoflurane for 6 h. Following exposure, cleaved caspase 3, expression of EGFP and differential maturational markers were quantified and compared with unanesthetized littermates. Electrophysiological properties of EGFP+ and EGFP− cells in the subgranular zone and the inner half of the granule cell layer were recorded by whole-cell patch-clamp. We found that sevoflurane significantly increased apoptosis of POMC-EGFP+ granule cells that accounted for approximate 1/3 of all apoptotic cells in dentate gyrus. Apoptotic EGFP− granule cells more frequently expressed the immature neuronal marker calretinin (75.4% vs 45.0%, P < 0.001) and less frequently the late progenitor marker NeuroD1 (21.9% vs 87.9%, P < 0.001) than EGFP+ granule cells. Although EGFP− granule cells were more mature in immunostaining than EGFP+ granule cells, their electrophysiological properties partially overlapped in terms of input resistance, resting membrane potential and action potential amplitude. Our results revealed the POMC stage, when GABA acts as an excitatory neurotransmitter, only partly captures susceptibility to anesthetic neurotoxicity, suggesting the vulnerable window of anesthesia-induced neuroapoptosis extends from the end of POMC+ stage to the post-POMC+ stage when depolarizing glutamatergic inputs emerge.

Polycomb Protein EED Regulates Neuronal Differentiation through Targeting SOX11 in Hippocampal Dentate Gyrus.

SummaryEED (embryonic ectoderm development) is a core component of the Polycomb repressive complex 2 (PRC2) which catalyzes the methylation of histone H3 lysine 27 (H3K27) during the process of self-renewal, proliferation, and differentiation of embryonic stem cells. However, its function in the mammalian nervous system remains unexplored. Here, we report that loss of EED in the brain leads to postnatal lethality, impaired neuronal differentiation, and malformation of the dentate gyrus. Overexpression of Sox11, a downstream target of EED through interaction with H3K27me1, restores the neuronal differentiation capacity of EED-ablated neural stem/progenitor cells (NSPCs). Interestingly, downregulation of Cdkn2a, another downstream target of EED which is regulated in an H3K27me3-dependent manner, reverses the proliferation defect of EED-ablated NSPCs. Taken together, these findings established a critical role of EED in the development of hippocampal dentate gyrus, which might shed new light on the molecular mechanism of intellectual disability in patients with EED mutations.

Suppressor of fused controls perinatal expansion and quiescence of future dentate adult neural stem cells.

Adult hippocampal neurogenesis requires the quiescent neural stem cell (NSC) pool to persist lifelong. However, establishment and maintenance of quiescent NSC pools during development is not understood. Here, we show that Suppressor of Fused (Sufu) controls establishment of the quiescent NSC pool during mouse dentate gyrus (DG) development by regulating Sonic Hedgehog (Shh) signaling activity. Deletion of Sufu in NSCs early in DG development decreases Shh signaling activity leading to reduced proliferation of NSCs, resulting in a small quiescent NSC pool in adult mice. We found that putative adult NSCs proliferate and increase their numbers in the first postnatal week and subsequently enter a quiescent state towards the end of the first postnatal week. In the absence of Sufu, postnatal expansion of NSCs is compromised, and NSCs prematurely become quiescent. Thus, Sufu is required for Shh signaling activity ensuring expansion and proper transition of NSC pools to quiescent states during DG development.

Identification of aberrantly methylated differentially expressed genes in age-related macular degeneration

DNA methylation plays a significant role in many diseases. Age-related macular degeneration (AMD) is a leading cause of vision loss for people aged 50 years and above, but the etiology and pathogenesis are largely unknown. This study aimed to identify the aberrantly methylated differentially expressed genes (DEGs) in AMD and predict the related pathways on the basis of public data.Aberrant methylation can influence the functions of key genes by altering their expression. Here, we found out DEGs by overlapping public microarray data (GSE29801 and GSE102952). Functional and enrichment analyses of selected genes were performed using the DAVID database. Subsequently, protein–protein interaction (PPI) networks were constructed by using STRING and visualized in cytoscape to determine hub genes. Finally, we collected AMD patients’ blood samples to identify the methylation statuses of these hub genes by using methylated DNA immunoprecipitation.In total, 156 hypermethylation-low expression genes and 127 hypomethylation-high expression genes were predicted. The hypermethylation-low expression genes were enriched in biological processes of response to cardiac conduction, ATP binding, and cell–cell junction assembly. The top 5 hub genes of the PPI network were HSP90AA1, HSPA1L, HSPE1, HSP90B1, and NOP56. Meanwhile, the hypomethylation-high expression genes were enriched in the biological processes of response to positive regulation of the MAPK cascade, actin cytoskeleton reorganization, dentate gyrus development, and cell migration. The top 5 hub genes of this PPI network were PIK3R1, EZR, IGF2, SLC2A1, and CDKN1C. Moreover, the methylation statuses of NOP56, EZR, IGF2, SLC2A1, CDKN1C were confirmed to be altered in the blood of AMD patients.This study indicated possible aberrantly methylated DEGs and differentially expressed pathways in AMD by bioinformatics analysis, providing novel insights for unraveling the pathogenesis of AMD. Hub genes, including NOP56, EZR, IGF2, SLC2A1, CDKN1C, might serve as aberrant methylation-based candidate biomarkers for AMD in future applications.

Early life stress delays hippocampal development and diminishes the adult stem cell pool in mice

Early life stress predisposes to mental illness and behavioral dysfunction in adulthood, but the mechanisms underlying these persistent effects are poorly understood. Stress throughout life impairs the structure and function of the hippocampus, a brain system undergoing considerable development in early life. The long-term behavioral consequences of early life stress may therefore be due in part to interference with hippocampal development, in particular with assembly of the dentate gyrus (DG) region of the hippocampus. We investigated how early life stress produces long-term alterations in DG structure by examining DG assembly and the generation of a stable adult stem cell pool in routine housing and after stress induced by the limited bedding/nesting paradigm in mice. We found that early life stress leads to a more immature, proliferative DG than would be expected for the animal’s age immediately after stress exposure, suggesting that early life stress delays DG development. Adult animals exposed to early life stress exhibited a reduction in the number of DG stem cells, but unchanged neurogenesis suggesting a depletion of the stem cell pool with compensation in the birth and survival of adult-born neurons. These results suggest a developmental mechanism by which early life stress can induce long-term changes in hippocampal function by interfering with DG assembly and ultimately diminishing the adult stem cell pool.

Perinatal exposure to the SSRI paroxetine alters the methylome landscape of the developing dentate gyrus.

Evidence in humans and rodents suggests that perinatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants can have serious long-term consequences in offspring exposed in utero or infancy via breast milk. In spite of this, there is limited knowledge of how perinatal SSRI exposure impacts brain development and adult behaviour. Children exposed to SSRIs in utero exhibit increased internalizing behaviour and abnormal social behaviour between the ages of 3 and 6, and increased risk of depression in adolescence; however, the neurobiological changes underlying this behaviour are poorly understood. In rodents, perinatal SSRI exposure perturbs hippocampal gene expression and alters adult emotional behaviour (including increased depression-like behaviour). The present study demonstrates that perinatal exposure to the SSRI paroxetine leads to DNA hypomethylation and reduces DNA methyltransferase 3a (Dnmt3a) mRNA expression in the hippocampus during the second and third weeks of life. Next-generation sequencing identified numerous differentially methylated genomic regions, including altered methylation and transcription of several dendritogenesis-related genes. We then tested the hypothesis that transiently decreasing Dnmt3a expression in the early postnatal hippocampus would mimic the behavioural effects of perinatal SSRI exposure. We found that siRNA-mediated knockdown of Dnmt3a in the dentate gyrus during the second to third week of life produced greater depression-like behaviour in adult female (but not male) offspring, akin to the behavioural consequences of perinatal SSRI exposure. Overall, these data suggest that perinatal SSRI exposure may increase depression-like behaviours, at least in part, through reduced Dnmt3a expression in the developing hippocampus.

Ablation of proliferating neural stem cells during early life is sufficient to reduce adult hippocampal neurogenesis.

Environmental exposures during early life, but not during adolescence or adulthood, lead to persistent reductions in neurogenesis in the adult hippocampal dentate gyrus (DG). The mechanisms by which early life exposures lead to long-term deficits in neurogenesis remain unclear. Here, we investigated whether targeted ablation of dividing neural stem cells during early life is sufficient to produce long-term decreases in DG neurogenesis. Having previously found that the stem cell lineage is resistant to long-term effects of transient ablation of dividing stem cells during adolescence or adulthood (Kirshenbaum, Lieberman, Briner, Leonardo, & Dranovsky, ), we used a similar pharmacogenetic approach to target dividing neural stem cells for elimination during early life periods sensitive to environmental insults. We then assessed the Nestin stem cell lineage in adulthood. We found that the adult neural stem cell reservoir was depleted following ablation during the first postnatal week, when stem cells were highly proliferative, but not during the third postnatal week, when stem cells were more quiescent. Remarkably, ablating proliferating stem cells during either the first or third postnatal week led to reduced adult neurogenesis out of proportion to the changes in the stem cell pool, indicating a disruption of the stem cell function or niche following stem cell ablation in early life. These results highlight the first three postnatal weeks as a series of sensitive periods during which elimination of dividing stem cells leads to lasting alterations in adult DG neurogenesis and stem cell function. These findings contribute to our understanding of the relationship between DG development and adult neurogenesis, as well as suggest a possible mechanism by which early life experiences may lead to lasting deficits in adult hippocampal neurogenesis.

PDK1 Deficit Impairs the Development of the Dentate Gyrus in Mice.

3-Phosphoinositide-dependent protein kinase-1 (PDK1) is crucial for the development of the dentate gyrus (DG), the first gateway receiving afferent inputs from the entorhinal cortex. However, the role of PDK1 in DG development is unclear. In the present study, by crossing Pdk1fl/fl mice with the Emx1-cre line, we identified that the ablation of PDK1 disrupted the development of DG via decreasing the proliferation, and increasing the differentiation of dentate neural progenitor cells, downregulating AKT activity and upregulating GSK3β signaling. Moreover, PDK1 deletion disrupted the distribution of Reelin+ cells and decreased the level of Reelin mRNA which may contribute to the defective migration of progenitor cells and the disrupted radial glial scaffolds. Furthermore, the inhibition of GSK3β activity partially restored the decreased proliferation of primary neural stem cells in vitro. Taken together, our data indicated that the ablation of PDK1 affected the proliferation and differentiation of dentate neural progenitor cells in mice.

PlexinA2 Forward Signaling through Rap1 GTPases Regulates Dentate Gyrus Development and Schizophrenia-like Behaviors

SUMMARYDentate gyrus (DG) development requires specification of granule cell (GC) progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs is regulated by Sema5A signaling through PlxnA2 and requires a functional PlxnA2 GTPase-activating protein (GAP) domain and Rap1 small GTPases. In adult Plxna2−/− but not Plxna2-GAP-deficient mice, the dentate GC layer is severely malformed, neurogenesis is compromised, and mossy fibers form aberrant synaptic boutons within CA3. Behavioral studies with Plxna2−/− mice revealed deficits in associative learning, sociability, and sensorimotor gating—traits commonly observed in neuropsychiatric disorder. Remarkably, while morphological defects are minimal in Plxna2-GAP-deficient brains, defects in fear memory and sensorimotor gating persist. Since allelic variants of human PLXNA2 and RAP1 associate with schizophrenia, our studies identify a biochemical pathway important for brain development and mental health.

Dentate granule progenitor cell properties are rapidly altered soon after birth.

Neurogenesis occurs during the embryonic period and ceases soon after birth in the neocortex, but continues to occur in the hippocampus even in the adult. The embryonic neocortex has radial glia or progenitor cells expressing brain lipid-binding protein (BLBP), whereas the adult hippocampus has radial granule progenitor cells expressing BLBP and glial fibrillary acidic protein (GFAP) in the subgranular zone. We previously found that embryonic hippocampal granule progenitor cells express GFAP, but not BLBP, indicating that these cells are different from both embryonic neocortical and adult granule progenitor cells. In the present study, as the first step towards understanding the mechanism of persistent hippocampal neurogenesis, we aimed to determine the stage at which embryonic-type granule progenitors become adult-type progenitors using mouse Gfap-GFP transgenic mice. During the embryonic stages, Gfap-GFP-positive (Gfap-GFP+) cells were distributed in the entire developing dentate gyrus (DG), whereas BLBP-positive (BLBP+) cells were mainly present in the fimbria and subpial region, and to some extent in the DG. Up to postnatal day 0 (P0), double-positive cells were scarcely detected. However, at P1, one-third of the Gfap-GFP+ cells in the DG suddenly began to weakly express BLBP. Thereafter, Gfap-GFP+/BLBP+ cells rapidly increased in number, and extended their radial processes in the inner granular cell layer. At P14 and in the adult, two-thirds of the Gfap-GFP+ cells in the subgranular zone showed BLBP immunoreactivity. These results suggest that the properties of hippocampal granule progenitor cells are rapidly altered from an embryonic to adult type soon after birth.

BACE1 Deficiency Causes Abnormal Neuronal Clustering in the Dentate Gyrus.

SummaryBACE1 is validated as Alzheimer's β-secretase and a therapeutic target for Alzheimer's disease. In examining BACE1-null mice, we discovered that BACE1 deficiency develops abnormal clusters of immature neurons, forming doublecortin-positive neuroblasts, in the developing dentate gyrus, mainly in the subpial zone (SPZ). Such clusters were rarely observed in wild-type SPZ and not reported in other mouse models. To understand their origins and fates, we examined how neuroblasts in BACE1-null SPZ mature and migrate during early postnatal development. We show that such neuroblasts are destined to form Prox1-positive granule cells in the dentate granule cell layer, and mainly mature to form excitatory neurons, but not inhibitory neurons. Mechanistically, higher levels of reelin potentially contribute to abnormal neurogenesis and timely migration in BACE1-null SPZ. Altogether, we demonstrate that BACE1 is a critical regulator in forming the dentate granule cell layer through timely maturation and migration of SPZ neuroblasts.

Autism spectrum disorder-associated genes and the development of dentate granule cells.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe clinical symptoms such as the deficiency of the social communication, repetitive and stereotyped behaviors, and restricted interests. Although complex genetic and environmental factors are thought to contribute to the development of ASD, the precise etiologies are largely unknown. Neuroanatomical observations have been made of developmental abnormalities in different brain regions, including dentate gyrus of hippocampus, which is widely accepted as the center for learning and memory. However, little is known about what roles ASD-associated genes play in the development of hippocampal dentate granule cells. In this article, we summarized functions and pathophysiological significance of 6 representative ASD-associated genes, SEMA5A, PTEN, NLGN, EN-2, FMR1, and MECP2, by focusing on the development of dentate gyrus. We then introduced a recently developed gene transfer method directed to neonatal dentate granule cells. This new method will be useful for elucidating physiological as well as pathophysiological significance of ASD-associated genes in the development of hippocampal formation.

Transmembrane protein 108 is required for glutamatergic transmission in dentate gyrus

Neurotransmission in dentate gyrus (DG) is critical for spatial coding, learning memory, and emotion processing. Although DG dysfunction is implicated in psychiatric disorders, including schizophrenia, underlying pathological mechanisms remain unclear. Here we report that transmembrane protein 108 (Tmem108), a novel schizophrenia susceptibility gene, is highly enriched in DG granule neurons and its expression increased at the postnatal period critical for DG development. Tmem108 is specifically expressed in the nervous system and enriched in the postsynaptic density fraction. Tmem108-deficient neurons form fewer and smaller spines, suggesting that Tmem108 is required for spine formation and maturation. In agreement, excitatory postsynaptic currents of DG granule neurons were decreased in Tmem108 mutant mice, indicating a hypofunction of glutamatergic activity. Further cell biological studies indicate that Tmem108 is necessary for surface expression of AMPA receptors. Tmem108-deficient mice display compromised sensorimotor gating and cognitive function. Together, these observations indicate that Tmem108 plays a critical role in regulating spine development and excitatory transmission in DG granule neurons. When Tmem108 is mutated, mice displayed excitatory/inhibitory imbalance and behavioral deficits relevant to schizophrenia, revealing potential pathophysiological mechanisms of schizophrenia.

DNA Methyltransferase 1 Is Indispensable for Development of the Hippocampal Dentate Gyrus.

Development of the hippocampal dentate gyrus (DG) in the mammalian brain is achieved through multiple processes during late embryonic and postnatal stages, with each developmental step being strictly governed by extracellular cues and intracellular mechanisms. Here, we show that the maintenance DNA methyltransferase 1 (Dnmt1) is critical for development of the DG in the mouse. Deletion of Dnmt1 in neural stem cells (NSCs) at the beginning of DG development led to a smaller size of the granule cell layer in the DG. NSCs lacking Dnmt1 failed to establish proper radial processes or to migrate into the subgranular zone, resulting in aberrant neuronal production in the molecular layer of the DG and a reduction of integrated neurons in the granule cell layer. Interestingly, prenatal deletion of Dnmt1 in NSCs affected not only the developmental progression of the DG but also the properties of NSCs maintained into adulthood: Dnmt1-deficient NSCs displayed impaired neurogenic ability and proliferation. We also found that Dnmt1 deficiency in NSCs decreased the expression of Reelin signaling components in the developing DG and increased that of the cell cycle inhibitors p21 and p57 in the adult DG. Together, these findings led us to propose that Dnmt1 functions as a key regulator to ensure the proper development of the DG, as well as the proper status of NSCs maintained into adulthood, by modulating extracellular signaling and intracellular mechanisms. Here, we provide evidence that Dnmt1 is required for the proper development of the hippocampal dentate gyrus (DG). Deletion of Dnmt1 in neural stem cells (NSCs) at an early stage of DG development impaired the ability of NSCs to establish secondary radial glial scaffolds and to migrate into the subgranular zone of the DG, leading to aberrant neuronal production in the molecular layer, increased cell death, and decreased granule neuron production. Prenatal deletion of Dnmt1 in NSCs also induced defects in the proliferation and neurogenic ability of adult NSCs. Furthermore, we found that Dnmt1 regulates the expression of key extracellular signaling components during developmental stages while modulating intracellular mechanisms for proliferation and neuronal production of NSCs in the adult.

GSK3β Overexpression in Dentate Gyrus Neural Precursor Cells Expands the Progenitor Pool and Enhances Memory Skills

In restricted areas of the adult brain, like the subgranular zone of the dentate gyrus (DG), there is continuous production of new neurons. This process, named adult neurogenesis, is involved in important cognitive functions such as memory and learning. It requires the presence of newborn neurons that arise from neuronal stem cells, which divide and differentiate through successive stages in adulthood. In this work, we demonstrate that overexpression of glycogen synthase kinase (GSK) 3β in neural precursor cells (NPCs) using the glial fibrillary acidic protein promoter during DG development produces an increase in the neurogenic process, increasing NPCs numbers. Moreover, the transgenic mice show higher DG volume and increased number of mature granule neurons. In an attempt to compensate for these alterations, glial fibrillary acidic protein/GSK3β-overexpressing mice show increased levels of Dkk1 and sFRP3, two inhibitors of the Wnt-frizzled complex. We have also found behavioral differences between wild type and transgenic mice, indicating a higher rating in memory tasks for GSK3β-overexpressing mice compared with wild type mice. These data indicate that GSK3β is a crucial kinase in NPC physiology and suggest that this molecule plays a key role in the correct development of DG and adult neurogenesis in this region.

Editorial: Molecular Mechanisms for Reprogramming Hippocampal Development and Function by Early-Life Stress.

Editorial: Molecular Mechanisms for Reprogramming Hippocampal Development and Function by Early-Life Stress.