Notch1 deficiency in postnatal neural progenitor cells in the dentate gyrus leads to emotional and cognitive impairment

2017 ◽  
Vol 31 (10) ◽  
pp. 4347-4358 ◽  
Author(s):  
Shufang Feng ◽  
Tianyao Shi ◽  
Jiangxia Qiu ◽  
Haihong Yang ◽  
Yan Wu ◽  
...  
Hippocampus ◽  
2011 ◽  
Vol 22 (6) ◽  
pp. 1220-1224 ◽  
Author(s):  
Orly Lazarov ◽  
Michael P. Demars ◽  
Kai Da Tommy Zhao ◽  
Haroon M. Ali ◽  
Vanessa Grauzas ◽  
...  

2005 ◽  
Vol 22 (8) ◽  
pp. 1928-1941 ◽  
Author(s):  
Takashi Namba ◽  
Hideki Mochizuki ◽  
Masafumi Onodera ◽  
Yoshikuni Mizuno ◽  
Hideo Namiki ◽  
...  

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Rui Lan Zhang ◽  
Wanlong Pan ◽  
Xiaoming Zhang ◽  
Xianshuang Liu ◽  
Julie Landschoot-Ward ◽  
...  

Introduction: Dicer processes precursor miRNAs into mature miRNAs. We have demonstrated that conditional knockout of Dicer (Dicer/Cko) in adult neural progenitor cells (NPCs) impairs neurogenesis and cognitive function. The present study tested the hypothesis that cerebral endothelial-derived exosomes carrying mature miRNAs promote neurogenesis and improve cognitive function by communication with NPCs in Dicer/Cko mice. Methods and Results: Exosomes harvested from cultured cerebral endothelial cells (CEC-Ex, 1x10 9 exosomes) were intranasally administered twice a week for two consecutive weeks into mice (n=10) with conditional ablation of Dicer (Dicer/Cko) in NPCs ( Ascl1- CreER :Dicer flox/flox ). Dicer/Cko mice treated with saline (n=12) were used as control. Cognitive tests were performed, including Morris Water Maze (MWM) for hippocampal related learning and memory, odor-based novelty recognition for olfactory memory, and social interaction for memory of interactions with novel conspecifics. Compared to wild-type mice, Dicer/Cko mice treated with saline exhibited substantial cognitive impairment. The CEC-Ex treatment diminished cognitive deficits and these mice exhibited an increase of 40% more time spent in the correct quadrant (p<0.05) of the MWM, and increased time exploring new odor objects (71±9% vs 41 ±10% saline, p<0.05) and increased time in contact with a strange mouse during the sociability test. Using a Cre/flox reporter approach, we found that the exosomes carrying Cre mRNA entered NPCs in the subventricular zone (SVZ) and dentate gyrus (DG). The CEC-Ex treatment significantly (p<0.05) increased BrdU + NPCs (20 ± 1% vs 14 ± 2%, SVZ, 16±1% vs 12±3%, DG ) and DCX+ neuroblasts (27 ± 2% vs 22 ± 3%, SVZ, 33 ± 2% vs 25 ± 3%, DG), and reduced apoptotic cells by more than 50% in these two areas. RT-PCR analysis showed that Dicer/Cko mice exhibited substantial reduction of mature miRNAs that regulate neurogenesis including miR-124, -146a and -17-92 cluster in NPCs, whereas the CEC-Ex treatment increased these mature miRNAs in Dicer/Cko NPCs. Conclusion: The CEC-Ex can reverse impaired neurogenesis and cognitive function induced by ablation of Dicer, which is likely attributed to the delivery of mature miRNAs into NPCs by CEC-Ex.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Brenna Hourigan ◽  
Spencer D. Balay ◽  
Graydon Yee ◽  
Saloni Sharma ◽  
Qiumin Tan

AbstractNew neurons continuously arise from neural progenitor cells in the dentate gyrus of the adult hippocampus to support ongoing learning and memory formation. To generate functional adult-born neurons, neural progenitor cells proliferate to expand the precursor cell pool and differentiate into neurons. Newly generated cells then undergo postmitotic maturation to migrate to their final destination and develop elaborate dendritic branching, which allows them to receive input signals. Little is known about factors that regulate neuronal differentiation, migration, and dendrite maturation during adult hippocampal neurogenesis. Here, we show that the transcriptional repressor protein capicua (CIC) exhibits dynamic expression in the adult dentate gyrus. Conditional deletion of Cic from the mouse dentate gyrus compromises the adult neural progenitor cell pool without altering their proliferative potential. We further demonstrate that the loss of Cic impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons. Our study uncovers a previously unrecognized role of CIC in neurogenesis of the adult dentate gyrus.


Author(s):  
Miguel V. Guerra ◽  
Matías I. Cáceres ◽  
Andrea Herrera-Soto ◽  
Sebastián B. Arredondo ◽  
Manuel Varas-Godoy ◽  
...  

In the dentate gyrus of the adult hippocampus new neurons are generated from neural precursor cells through different stages including proliferation and differentiation of neural progenitor cells and maturation of newborn neurons. These stages are controlled by the expression of specific transcription factors and epigenetic mechanisms, which together orchestrate the progression of the neurogenic process. However, little is known about the involvement of histone posttranslational modifications, a crucial epigenetic mechanism in embryonic neurogenesis that regulates fate commitment and neuronal differentiation. During embryonic development, the repressive modification trimethylation of histone H3 on lysine 9 (H3K9me3) contributes to the cellular identity of different cell-types. However, the role of this modification and its H3K9 methyltransferases has not been elucidated in adult hippocampal neurogenesis. We determined that during the stages of neurogenesis in the adult mouse dentate gyrus and in cultured adult hippocampal progenitors (AHPs), there was a dynamic change in the expression and distribution of H3K9me3, being enriched at early stages of the neurogenic process. A similar pattern was observed in the hippocampus for the dimethylation of histone H3 on lysine 9 (H3K9me2), another repressive modification. Among H3K9 methyltransferases, the enzymes Suv39h1 and Suv39h2 exhibited high levels of expression at early stages of neurogenesis and their expression decreased upon differentiation. Pharmacological inhibition of these enzymes by chaetocin in AHPs reduced H3K9me3 and concomitantly decreased neuronal differentiation while increasing proliferation. Moreover, Suv39h1 and Suv39h2 knockdown in newborn cells of the adult mouse dentate gyrus by retrovirus-mediated RNA interference impaired neuronal differentiation of progenitor cells. Our results indicate that H3K9me3 and H3K9 methyltransferases Suv39h1 and Suv39h2 are critically involved in the regulation of adult hippocampal neurogenesis by controlling the differentiation of neural progenitor cells.


2017 ◽  
Vol 36 (09) ◽  
pp. 240-245 ◽  
Author(s):  
Ju-Yoon Yoon ◽  
Brett Danielson ◽  
Derek Mathis ◽  
Jason Karamchandani ◽  
David G. Munoz

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