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

Hippocampus ◽  
2018 ◽  
Vol 28 (8) ◽  
pp. 586-601 ◽  
Author(s):  
Mary Youssef ◽  
Varsha S. Krish ◽  
Greer S. Kirshenbaum ◽  
Piray Atsak ◽  
Tamara J. Lass ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Early Life ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

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

2018 ◽  
Author(s):  
Mary Youssef ◽  
Varsha S. Krish ◽  
Greer S. Kirshenbaum ◽  
Piray Atsak ◽  
Tamara J. Lass ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Early Life ◽  
Cell Function ◽  
Cell Lineage ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Stem Cell Lineage

AbstractEnvironmental 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 et al., 2014), 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.

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.

scholarly journals Ablation of the microRNA‐17‐92 cluster in neural stem cells diminishes adult hippocampal neurogenesis and cognitive function

2019 ◽  
Vol 33 (4) ◽  
pp. 5257-5267 ◽  
Author(s):  
Wan Long Pan ◽  
Michael Chopp ◽  
Baoyan Fan ◽  
Ruilan Zhang ◽  
Xinli Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cognitive Function ◽  
Neural Stem Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

scholarly journals Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits

IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S487
Author(s):  
Seonghee Jung ◽  
Seongwon Choe ◽  
Hanwoong Woo ◽  
Hyeonjeong Jeong ◽  
Hyun-Kyu An ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Chronic Stress ◽  
Cognitive Deficits ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

scholarly journals Circadian and ultradian glucocorticoid rhythmicity: Implications for the effects of glucocorticoids on neural stem cells and adult hippocampal neurogenesis

2016 ◽  
Vol 41 ◽  
pp. 44-58 ◽  
Author(s):  
Carlos P. Fitzsimons ◽  
Joe Herbert ◽  
Marijn Schouten ◽  
Onno C. Meijer ◽  
Paul J. Lucassen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis

scholarly journals Active Fraction Combination From Liuwei Dihuang Decoction Improves Adult Hippocampal Neurogenesis and Neurogenic Microenvironment in Cranially Irradiated Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingxiao Wei ◽  
Shufang Feng ◽  
Lin Zhang ◽  
Chen Wang ◽  
Shasha Chu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Dorsal Hippocampus ◽  
Cranial Irradiation ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Active Fraction ◽  
Cranial Radiotherapy ◽  
Contextual Fear ◽  
Immature Neurons

Background: Cranial radiotherapy is clinically used in the treatment of brain tumours; however, the consequent cognitive and emotional dysfunctions seriously impair the life quality of patients. LW-AFC, an active fraction combination extracted from classical traditional Chinese medicine prescription Liuwei Dihuang decoction, can improve cognitive and emotional dysfunctions in many animal models; however, the protective effect of LW-AFC on cranial irradiation–induced cognitive and emotional dysfunctions has not been reported. Recent studies indicate that impairment of adult hippocampal neurogenesis (AHN) and alterations of the neurogenic microenvironment in the hippocampus constitute critical factors in cognitive and emotional dysfunctions following cranial irradiation. Here, our research further investigated the potential protective effects and mechanisms of LW-AFC on cranial irradiation–induced cognitive and emotional dysfunctions in mice.Methods: LW-AFC (1.6 g/kg) was intragastrically administered to mice for 14 days before cranial irradiation (7 Gy γ-ray). AHN was examined by quantifying the number of proliferative neural stem cells and immature neurons in the dorsal and ventral hippocampus. The contextual fear conditioning test, open field test, and tail suspension test were used to assess cognitive and emotional functions in mice. To detect the change of the neurogenic microenvironment, colorimetry and multiplex bead analysis were performed to measure the level of oxidative stress, neurotrophic and growth factors, and inflammation in the hippocampus.Results: LW-AFC exerted beneficial effects on the contextual fear memory, anxiety behaviour, and depression behaviour in irradiated mice. Moreover, LW-AFC increased the number of proliferative neural stem cells and immature neurons in the dorsal hippocampus, displaying a regional specificity of neurogenic response. For the neurogenic microenvironment, LW-AFC significantly increased the contents of superoxide dismutase, glutathione peroxidase, glutathione, and catalase and decreased the content of malondialdehyde in the hippocampus of irradiated mice, accompanied by the increase in brain-derived neurotrophic factor, insulin-like growth factor-1, and interleukin-4 content. Together, LW-AFC improved cognitive and emotional dysfunctions, promoted AHN preferentially in the dorsal hippocampus, and ameliorated disturbance in the neurogenic microenvironment in irradiated mice.Conclusion: LW-AFC ameliorates cranial irradiation–induced cognitive and emotional dysfunctions, and the underlying mechanisms are mediated by promoting AHN in the dorsal hippocampus and improving the neurogenic microenvironment. LW-AFC might be a promising therapeutic agent to treat cognitive and emotional dysfunctions in patients receiving cranial radiotherapy.

scholarly journals Norbin ablation results in defective adult hippocampal neurogenesis and depressive-like behavior in mice

2015 ◽  
Vol 112 (31) ◽  
pp. 9745-9750 ◽  
Author(s):  
Hong Wang ◽  
Jennifer Warner-Schmidt ◽  
Santiago Varela ◽  
Grigori Enikolopov ◽  
Paul Greengard ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Fate ◽  
Adult Neurogenesis ◽  
Metabotropic Glutamate Receptors ◽  
Forced Swim Test ◽  
Critical Role ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Cell Contact

Adult neurogenesis in the hippocampus subgranular zone is associated with the etiology and treatment efficiency of depression. Factors that affect adult hippocampal neurogenesis have been shown to contribute to the neuropathology of depression. Glutamate, the major excitatory neurotransmitter, plays a critical role in different aspects of neurogenesis. Of the eight metabotropic glutamate receptors (mGluRs), mGluR5 is the most highly expressed in neural stem cells. We previously identified Norbin as a positive regulator of mGluR5 and showed that its expression promotes neurite outgrowth. In this study, we investigated the role of Norbin in adult neurogenesis and depressive-like behaviors using Norbin-deficient mice. We found that Norbin deletion significantly reduced hippocampal neurogenesis; specifically, the loss of Norbin impaired the proliferation and maturation of newborn neurons without affecting cell-fate specification of neural stem cells/neural progenitor cells (NSCs/NPCs). Norbin is highly expressed in the granular neurons in the dentate gyrus of the hippocampus, but it is undetectable in NSCs/NPCs or immature neurons, suggesting that the effect of Norbin on neurogenesis is likely caused by a nonautonomous niche effect. In support of this hypothesis, we found that the expression of a cell–cell contact gene, Desmoplakin, is greatly reduced in Norbin-deletion mice. Moreover, Norbin-KO mice show an increased immobility in the forced-swim test and the tail-suspension test and reduced sucrose preference compared with wild-type controls. Taken together, these results show that Norbin is a regulator of adult hippocampal neurogenesis and that its deletion causes depressive-like behaviors.

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.

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