scholarly journals Saikosaponin‐d impedes hippocampal neurogenesis and causes cognitive deficits by inhibiting the survival of neural stem/progenitor cells via neurotrophin receptor signaling in mice

2020 ◽  
Vol 10 (8) ◽  
Author(s):  
Tingting Qin ◽  
Ziqiao Yuan ◽  
Jiayu Yu ◽  
Xinxin Fu ◽  
Xueyang Deng ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cognitive Deficits ◽  
Hippocampal Neurogenesis ◽  
Neurotrophin Receptor ◽  
Receptor Signaling ◽  
Neural Stem Progenitor Cells

Mitochondrial dysfunction-induced KDM5A degradation impairs adult hippocampal neurogenesis in Alzheimer’s disease

2020 ◽  
Author(s):  
Dong Kyu Kim ◽  
Hyobin Jeong ◽  
Jingi Bae ◽  
Moon-Yong Cha ◽  
Moonkyung Kang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mitochondrial Dysfunction ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Amyloid Pathology ◽  
Neural Stem Progenitor Cells

Abstract Background Adult hippocampal neurogenesis (AHN) is a process of continuously generating functional mature neurons from neural stem cells in the dentate gyrus. In Alzheimer’s disease (AD) brains, amyloid pathology has deleterious effects on AHN, but molecular mechanisms for dysregulated AHN are unclear. Mitochondria of neural stem/progenitor cells play crucial roles in determining cell fate. Since mitochondrial dysfunction by amyloid pathology is the typical symptom of AD pathogenesis, we aim to study whether mitochondrial dysfunction of neural stem/progenitor cells by amyloid pathology causes the impairment of AHN, and elucidate the molecular mechanism of the phenomenon. Methods To investigate the effect of mitochondrial dysfunction of neural stem/progenitor cells on neuronal differentiation, we expressed mitochondria-targeted amyloid beta (mitoAβ) in neural stem/progenitor cells in vitro and in vivo. Proteomic analysis of the hippocampal tissue implicated mitochondrial dysfunction by mitoAβ as a cause of AHN deficits. We identified epigenetic regulators of neural progenitor cells that are regulated by mitoAβ expression or drug-induced mitochondrial toxicity and proposed a link between mitochondria and AHN. Results Amyloid pathology characteristically inhibited the neuronal differentiation stage, not the proliferation of neural stem/progenitor cells during AHN in early AD model mice. Mitochondrial dysfunction in neural stem/progenitor cells by expressing mitoAβ inhibited the neuronal differentiation and AHN with cognitive impairment. Mechanistic studies revealed that lysine demethylase 5A (KDM5A) was involved in the neuronal differentiation and could be degraded by mitochondrial dysfunction in neural progenitor cells, thereby inhibiting the differentiation and cognitive functions. Conclusions These results reveal the new role of KDM5A as a mediator of retrograde signaling, reflecting mitochondrial status, and that the decrease of KDM5A in neural progenitor cells by mitochondrial dysfunction impairs the neuronal differentiation and AHN, finally leading to memory deficits. These findings and its relationship to mitochondrial dysfunction suggest that mitochondrial failure in neural progenitor cells by amyloid pathology closely associates with reduced AHN in AD.

scholarly journals Baicalin Regulates Neuronal Fate Decision in Neural Stem/Progenitor Cells and Stimulates Hippocampal Neurogenesis in Adult Rats

2013 ◽  
Vol 19 (3) ◽  
pp. 154-162 ◽  
Author(s):  
Peng-Wei Zhuang ◽  
Guang-Zhi Cui ◽  
Yan-Jun Zhang ◽  
Mi-Xia Zhang ◽  
Hong Guo ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Rats ◽  
Neuronal Fate ◽  
Neural Stem Progenitor Cells ◽  
Fate Decision

scholarly journals Epigenetic regulation of the stem cell mitogen Fgf-2 by Mbd1 in adult neural stem/progenitor cells. VOLUME 283 (2008) PAGES 27644-27652

2009 ◽  
Vol 284 (13) ◽  
pp. 8995
Author(s):  
Xuekun Li ◽  
Basam Z. Barkho ◽  
Jinfeng Bao ◽  
Yuping Luo ◽  
Richard D. Smrt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progenitor Cells ◽  
Epigenetic Regulation ◽  
Neural Stem Progenitor Cells ◽  
Cell Mitogen
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