Dynamic Fas signaling network regulates neural stem cell proliferation and memory enhancement

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Activation of Fas (CD95) is observed in various neurological disorders and can lead to both apoptosis and prosurvival outputs, yet how Fas signaling operates dynamically in the hippocampus is poorly understood. The optogenetic dissection of a signaling network can yield molecular-level explanations for cellular responses or fates, including the signaling dysfunctions seen in numerous diseases. Here, we developed an optogenetically activatable Fas that works in a physiologically plausible manner. Fas activation in immature neurons of the dentate gyrus triggered mammalian target of rapamycin (mTOR) activation and subsequent brain-derived neurotrophic factor secretion. Phosphorylation of extracellular signal-regulated kinase (Erk) in neural stem cells was induced under prolonged Fas activation. Repetitive activation of this signaling network yielded proliferation of neural stem cells and a transient increase in spatial working memory in mice. Our results demonstrate a novel Fas signaling network in the dentate gyrus and illuminate its consequences for adult neurogenesis and memory enhancement.
Publisher
AMER ASSOC ADVANCEMENT SCIENCE
Issue Date
2020-04
Language
English
Article Type
Article
Citation

SCIENCE ADVANCES, v.6, no.17

ISSN
2375-2548
DOI
10.1126/sciadv.aaz9691
URI
http://hdl.handle.net/10203/274332
Appears in Collection
BS-Journal Papers(저널논문)
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