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- W3113896250 abstract "Serotonin receptor 6 (5-HT6R), a typical G protein-coupled receptor (GPCR) mainly expressed in the neurogenic area with constitutive activity, is of particular interest as a promising target for emotional impairment. Here, we found that 5-HT6R was highly expressed in human NSCs and activation of the receptor promoted self-renewal of human NSCs, and thus induced the expansion and folding of human cerebral organoids; dysfunction of receptor or inhibition of its constitutive activity resulted in the premature differentiation of NSCs, which ultimately depleted the NSC pool. The following mechanistic study revealed that EPAC-CREB signaling was involved in 5-HT6R regulation. Furthermore, we showed that mice with genetic deletion of 5-HT6R or knockin A268R mutant presented depression-like behaviors and impaired hippocampal neurogenesis for progressive decrease of the NSC pool. Thus, this study indicates that the modulation of 5-HT6R and its constitutive activity may provide a therapeutic alternative to alleviate depression." @default.
- W3113896250 created "2021-01-05" @default.
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- W3113896250 date "2021-01-01" @default.
- W3113896250 modified "2023-10-09" @default.
- W3113896250 title "Constitutive Activity of Serotonin Receptor 6 Regulates Human Cerebral Organoids Formation and Depression-like Behaviors" @default.
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- W3113896250 doi "https://doi.org/10.1016/j.stemcr.2020.11.015" @default.
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