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

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.

Development of Neural Stem/Progenitor Cells from Human Brain by Transplantation into the Brains of Adult Rats

2004 ◽  
Vol 34 (7) ◽  
pp. 659-662 ◽  
Author(s):  
M. A. Aleksandrova ◽  
R. A. Poltavtseva ◽  
A. V. Revishchin ◽  
L. I. Korochkin ◽  
G. T. Sukhikh
Keyword(s):  
Human Brain ◽  
Progenitor Cells ◽  
Adult Rats ◽  
Neural Stem Progenitor Cells

Proliferation, migration, and differentiation of human neural stem/progenitor cells after transplantation into a rat model of traumatic brain injury

2004 ◽  
Vol 100 (1) ◽  
pp. 88-96 ◽  
Author(s):  
André Wennersten ◽  
Xia Meijer ◽  
Staffan Holmin ◽  
Lars Wahlberg ◽  
Tiit Mathiesen
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Corpus Callosum ◽  
Progenitor Cells ◽  
Adult Brain ◽  
Adult Rats ◽  
Double Labeling ◽  
Content Type ◽  
Neural Stem Progenitor Cells ◽  
Fine Print

Object. Cultures containing human neural stem and progenitor cells (neurospheres) have the capacity to proliferate and differentiate into the major phenotypes of the adult brain. These properties make them candidates for therapeutic transplantation in cases of neurological diseases that involve cell loss. In this study, long-term cultured and cryopreserved cells were transplanted into the traumatically injured rat brain to evaluate the potential for human neural stem/progenitor cells to survive and differentiate following traumatic injury. Methods. Neural stem/progenitor cell cultures were established from 10-week-old human forebrain. Immunosuppressed adult rats received a unilateral parietal cortical contusion injury, which was delivered using the weight-drop method. Immediately following the injury, these animals received transplants of neural stem/progenitor cells, which were placed close to the site of injury. Two or 6 weeks after the procedure, these animals were killed and their brains were examined by immunohistochemical analysis. At both 2 and 6 weeks postoperatively, the transplanted human cells were found in the perilesional zone, hippocampus, corpus callosum, and ipsilateral subependymal zone of the rats. Compared with the 2-week time point, an increased number of HuN-positive cells was observed at 6 weeks. In addition, at 6 weeks post—injury/transplantation, the cells were noted to cross the midline to the contralateral corpus callosum and into the contralateral cortex. Double labeling demonstrated neuronal and astrocytic, but not oligodendrocytic differentiation. Moreover, the cortex appeared to provide an environment that was less hospitable to neuronal differentiation than the hippocampus. Conclusions. This study shows that expandable human neural stem/progenitor cells survive transplantation, and migrate, differentiate, and proliferate in the injured brain. These cells could potentially be developed for transplantation therapy in cases of traumatic brain injury.

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