scholarly journals Fine processes of Nestin-GFP–positive radial glia-like stem cells in the adult dentate gyrus ensheathe local synapses and vasculature

2016 ◽  
Vol 113 (18) ◽  
pp. E2536-E2545 ◽  
Author(s):  
Jonathan Moss ◽  
Elias Gebara ◽  
Eric A. Bushong ◽  
Irene Sánchez-Pascual ◽  
Ruadhan O’Laoi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dentate Gyrus ◽  
Radial Glia ◽  
Molecular Layer ◽  
Cell Activity ◽  
Local Environment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Granule Cell Layer ◽  
Neurogenic Niche

Adult hippocampal neurogenesis relies on the activation of neural stem cells in the dentate gyrus, their division, and differentiation of their progeny into mature granule neurons. The complex morphology of radial glia-like (RGL) stem cells suggests that these cells establish numerous contacts with the cellular components of the neurogenic niche that may play a crucial role in the regulation of RGL stem cell activity. However, the morphology of RGL stem cells remains poorly described. Here, we used light microscopy and electron microscopy to examine Nestin-GFP transgenic mice and provide a detailed ultrastructural reconstruction analysis of Nestin-GFP–positive RGL cells of the dentate gyrus. We show that their primary processes follow a tortuous path from the subgranular zone through the granule cell layer and ensheathe local synapses and vasculature in the inner molecular layer. They share the ensheathing of synapses and vasculature with astrocytic processes and adhere to the adjacent processes of astrocytes. This extensive interaction of processes with their local environment could allow them to be uniquely receptive to signals from local neurons, glia, and vasculature, which may regulate their fate.

Neuroinflammation and physical exercise as modulators of adult hippocampal neural precursor cell behavior

2017 ◽  
Vol 29 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Martha Pérez-Domínguez ◽  
Luis B. Tovar-y-Romo ◽  
Angélica Zepeda
Keyword(s):  
Stem Cells ◽  
Physical Exercise ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Bone Morphogenetic Proteins ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Adult Neural Stem Cells ◽  
Neurogenic Niche ◽  
Glial Lineage

Abstract The dentate gyrus of the hippocampus is a plastic structure where adult neurogenesis constitutively occurs. Cell components of the neurogenic niche are source of paracrine as well as membrane-bound factors such as Notch, Bone Morphogenetic Proteins, Wnts, Sonic Hedgehog, cytokines, and growth factors that regulate adult hippocampal neurogenesis and cell fate decision. The integration and coordinated action of multiple extrinsic and intrinsic cues drive a continuous decision process: if adult neural stem cells remain quiescent or proliferate, if they take a neuronal or a glial lineage, and if new cells proliferate, undergo apoptotic death, or survive. The proper balance in the molecular milieu of this neurogenic niche leads to the production of neurons in a higher rate as that of astrocytes. But this rate changes in face of microenvironment modifications as those driven by physical exercise or with neuroinflammation. In this work, we first review the cellular and molecular components of the subgranular zone, focusing on the molecules, active signaling pathways and genetic programs that maintain quiescence, induce proliferation, or promote differentiation. We then summarize the evidence regarding the role of neuroinflammation and physical exercise in the modulation of adult hippocampal neurogenesis with emphasis on the activation of progression from adult neural stem cells to lineage-committed progenitors to their progeny mainly in murine models.

scholarly journals Lithium treatment and human hippocampal neurogenesis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alish B. Palmos ◽  
Rodrigo R. R. Duarte ◽  
Demelza M. Smeeth ◽  
Erin C. Hedges ◽  
Douglas F. Nixon ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Dentate Gyrus ◽  
Lithium Treatment ◽  
Molecular Layer ◽  
Empirical Support ◽  
Hippocampal Volume ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
High Dose ◽  
Cell Parameters

AbstractLithium is a first-line treatment for bipolar disorder, where it acts as a mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and that chronic use amongst bipolar disorder patients is associated with larger hippocampal volumes. Here, we tested the chronic effects of low (0.75 mM) and high (2.25 mM) doses of lithium on human hippocampal progenitor cells and used immunocytochemistry to investigate the effects of lithium on cell parameters implicated in neurogenesis. Corresponding RNA-sequencing and gene-set enrichment analyses were used to evaluate whether genes affected by lithium in our model overlap with those regulating the volume of specific layers of the dentate gyrus. We observed that high-dose lithium treatment in human hippocampal progenitors increased the generation of neuroblasts (P ≤ 0.01), neurons (P ≤ 0.01), and glia (P ≤ 0.001), alongside the expression of genes, which regulate the volume of the molecular layer of the dentate gyrus. This study provides empirical support that adult hippocampal neurogenesis and gliogenesis are mechanisms that could contribute to the effects of lithium on human hippocampal volume.

scholarly journals Brain Insulin-Like Growth Factor-I Directs the Transition from Stem Cells to Mature Neurons During Postnatal/Adult Hippocampal Neurogenesis

Stem Cells ◽  
2016 ◽  
Vol 34 (8) ◽  
pp. 2194-2209 ◽  
Author(s):  
Vanesa Nieto-Estévez ◽  
Carlos O. Oueslati-Morales ◽  
Lingling Li ◽  
James Pickel ◽  
Aixa V. Morales ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Brain Insulin ◽  
Mature Neurons ◽  
Growth Factor I

scholarly journals Metabolic tuning of inhibition regulates hippocampal neurogenesis in the adult brain

2020 ◽  
Vol 117 (41) ◽  
pp. 25818-25829
Author(s):  
Xinxing Wang ◽  
Hanxiao Liu ◽  
Johannes Morstein ◽  
Alexander J. E. Novak ◽  
Dirk Trauner ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Energy Homeostasis ◽  
Inhibitory Neuron ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Adult Hippocampal Neurogenesis ◽  
Neuron Activity ◽  
Adult Mice ◽  
Sphingosine 1 Phosphate ◽  
Underlying Mechanisms

Hippocampus-engaged behaviors stimulate neurogenesis in the adult dentate gyrus by largely unknown means. To explore the underlying mechanisms, we used tetrode recording to analyze neuronal activity in the dentate gyrus of freely moving adult mice during hippocampus-engaged contextual exploration. We found that exploration induced an overall sustained increase in inhibitory neuron activity that was concomitant with decreased excitatory neuron activity. A mathematical model based on energy homeostasis in the dentate gyrus showed that enhanced inhibition and decreased excitation resulted in a similar increase in neurogenesis to that observed experimentally. To mechanistically investigate this sustained inhibitory regulation, we performed metabolomic and lipidomic profiling of the hippocampus during exploration. We found sustainably increased signaling of sphingosine-1-phosphate, a bioactive metabolite, during exploration. Furthermore, we found that sphingosine-1-phosphate signaling through its receptor 2 increased interneuron activity and thus mediated exploration-induced neurogenesis. Taken together, our findings point to a behavior-metabolism circuit pathway through which experience regulates adult hippocampal neurogenesis.

scholarly journals Radial glial cells in the adult dentate gyrus: what are they and where do they come from?

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 277 ◽  
Author(s):  
Daniel A. Berg ◽  
Allison M. Bond ◽  
Guo-li Ming ◽  
Hongjun Song
Keyword(s):  
Stem Cells ◽  
Dentate Gyrus ◽  
Radial Glia ◽  
Neural Precursor Cells ◽  
Neural Precursor ◽  
Subgranular Zone ◽  
Adult Neural Stem Cell ◽  
Radial Glial Cells ◽  
Embryonic Origin ◽  
Radial Glial

Adult neurogenesis occurs in the dentate gyrus in the mammalian hippocampus. These new neurons arise from neural precursor cells named radial glia-like cells, which are situated in the subgranular zone of the dentate gyrus. Here, we review the emerging topic of precursor heterogeneity in the adult subgranular zone. We also discuss how this heterogeneity may be established during development and focus on the embryonic origin of the dentate gyrus and radial glia-like stem cells. Finally, we discuss recently developed single-cell techniques, which we believe will be critical to comprehensively investigate adult neural stem cell origin and heterogeneity.

scholarly journals JNK1 controls adult hippocampal neurogenesis and imposes cell-autonomous control of anxiety behaviour from the neurogenic niche

2016 ◽  
Vol 23 (2) ◽  
pp. 362-374 ◽  
Author(s):  
H Mohammad ◽  
F Marchisella ◽  
S Ortega-Martinez ◽  
P Hollos ◽  
K Eerola ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Autonomous Control ◽  
Adult Hippocampal Neurogenesis ◽  
Neurogenic Niche

scholarly journals Ghrelin gene products rescue cultured adult rat hippocampal neural stem cells from high glucose insult

2016 ◽  
Vol 57 (3) ◽  
pp. 171-184 ◽  
Author(s):  
Sehee Kim ◽  
Chanyang Kim ◽  
Seungjoon Park
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
High Glucose ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Gene Products ◽  
Growth Hormone Secretagogue ◽  
Phosphohistone H3 ◽  
Ghrelin Gene ◽  
Hippocampal Neural Stem Cells

Adult hippocampal neurogenesis is decreased in type 2 diabetes, and this impairment appears to be important in cognitive dysfunction. Previous studies suggest that ghrelin gene products (acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (OB)) promote neurogenesis. Therefore, we hypothesize that ghrelin gene products may reduce the harmful effects of high glucose (HG) on hippocampal neural stem cells (NSCs). The aim of this study was to investigate the role of these peptides on the survival of cultured hippocampal NSCs exposed to HG insult. Treatment of hippocampal NSCs with AG, UAG or OB inhibited HG-induced cell death and apoptosis. Exposure of cells to the growth hormone secretagogue receptor 1a antagonist abolished the protective effects of AG against HG toxicity, whereas those of UAG or OB were preserved. All three peptides attenuated HG-induced decrease in BrdU-labeled and phosphohistone-H3-labeled cells. We also investigated the effects of ghrelin gene products on the regulation of apoptosis at the mitochondrial level. AG, UAG or OB rescued hippocampal NSCs from HG insult by inhibiting intracellular and mitochondrial reactive oxygen species generation and stabilizing mitochondrial transmembrane potential. In addition, cells treated with ghrelin gene products showed an increased Bcl-2 and decreased Bax levels, thereby increasing the Bcl-2/Bax ratio, inhibiting cytochrome c release and preventing caspase-3 activation. Finally, AG-, UAG- or OB-mediated protection was dependent on the activities of adenosine monophosphate-activated protein kinase/uncoupling protein 2 pathway. Our data indicate that ghrelin gene products may act as survival factors that preserve mitochondrial function and inhibit oxidative stress-induced apoptosis.

Optical Recording Study of Granule Cell Activities in the Hippocampal Dentate Gyrus of Kainate-Treated Rats

2000 ◽  
Vol 83 (4) ◽  
pp. 2421-2430 ◽  
Author(s):  
Yo Otsu ◽  
Eiichi Maru ◽  
Hisayuki Ohata ◽  
Ichiro Takashima ◽  
Riichi Kajiwara ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Granule Cell ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Molecular Layer ◽  
Mossy Fibers ◽  
Optical Recording ◽  
Granule Cell Layer ◽  
Gabaergic Inhibition ◽  
Mossy Fiber Sprouting

In the epileptic hippocampus, newly sprouted mossy fibers are considered to form recurrent excitatory connections to granule cells in the dentate gyrus and thereby increase seizure susceptibility. To study the effects of mossy fiber sprouting on neural activity in individual lamellae of the dentate gyrus, we used high-speed optical recording to record signals from voltage-sensitive dye in hippocampal slices prepared from kainate-treated epileptic rats (KA rats). In 14 of 24 slices from KA rats, hilar stimulation evoked a large depolarization in almost the entire molecular layer in which granule cell apical dendrites are located. The signals were identified as postsynaptic responses because of their dependence on extracellular Ca2+. The depolarization amplitude was largest in the inner molecular layer (the target area of sprouted mossy fibers) and declined with increasing distance from the granule cell layer. In the inner molecular layer, a good correlation was obtained between depolarization size and the density of mossy fiber terminals detected by Timm staining methods. Blockade of GABAergic inhibition by bicuculline enlarged the depolarization in granule cell dendrites. Our data indicate that mossy fiber sprouting results in a large and prolonged synaptic depolarization in an extensive dendritic area and that the enhanced GABAergic inhibition partly masks the synaptic depolarization. However, despite the large dendritic excitation induced by the sprouted mossy fibers, seizurelike activity of granule cells was never observed, even when GABAergic inhibition was blocked. Therefore, mossy fiber sprouting may not play a critical role in epileptogenesis.

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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Hirofumi Noguchi ◽  
Jesse Garcia Castillo ◽  
Kinichi Nakashima ◽  
Samuel J Pleasure
Keyword(s):  
Stem Cells ◽  
Sonic Hedgehog ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Quiescent State ◽  
Shh Signaling ◽  
Suppressor Of Fused ◽  
Adult Mice ◽  
Adult Nscs ◽  
Signaling Activity

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.

scholarly journals Extracranial 125I Seed Implantation Allows Non-invasive Stereotactic Radioablation of Hippocampal Adult Neurogenesis in Guinea Pigs

2021 ◽  
Vol 15 ◽  
Author(s):  
Lily Wan ◽  
Rou-Jie Huang ◽  
Chen Yang ◽  
Jia-Qi Ai ◽  
Qian Zhou ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Hippocampal Formation ◽  
Dorsal Hippocampus ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Granule Cell Layer ◽  
Nuclear Antigen ◽  
Proliferating Cells ◽  
Seed Implantation ◽  
Non Invasive

Adult hippocampal neurogenesis (AHN) is important for multiple cognitive functions. We sort to establish a minimal or non-invasive radiation approach to ablate AHN using guinea pigs as an animal model. 125I seeds with different radiation dosages (1.0, 0.8, 0.6, 0.3 mCi) were implanted unilaterally between the scalp and skull above the temporal lobe for 30 and 60 days, with the radiation effect on proliferating cells, immature neurons, and mature neurons in the hippocampal formation determined by assessment of immunolabeled (+) cells for Ki67, doublecortin (DCX), and neuron-specific nuclear antigen (NeuN), as well as Nissl stain cells. Spatially, the ablation effect of radiation occurred across the entire rostrocaudal and largely the dorsoventral dimensions of the hippocampus, evidenced by a loss of DCX+ cells in the subgranular zone (SGZ) of dentate gyrus (DG) in the ipsilateral relative to contralateral hemispheres in reference to the 125I seed implant. Quantitatively, Ki67+ and DCX+ cells at the SGZ in the dorsal hippocampus were reduced in all dosage groups at the two surviving time points, more significant in the ipsilateral than contralateral sides, relative to sham controls. NeuN+ neurons and Nissl-stained cells were reduced in the granule cell layer of DG and the stratum pyramidale of CA1 in the groups with 0.6-mCi radiation for 60 days and 1.0 mCi for 30 and 60 days. Minimal cranial trauma was observed in the groups with 0.3– 1.0-mCi radiation at 60 days. These results suggest that extracranial radiation with 125I seed implantation can be used to deplete HAN in a radioactivity-, duration-, and space-controllable manner, with a “non-invasive” stereotactic ablation achievable by using 125I seeds with relatively low radioactivity dosages.

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