| First Author | Wang Q | Year | 2021 |
| Journal | Stem Cell Reports | Volume | 16 |
| Issue | 1 | Pages | 75-88 |
| PubMed ID | 33357407 | Mgi Jnum | J:302649 |
| Mgi Id | MGI:6509366 | Doi | 10.1016/j.stemcr.2020.11.015 |
| Citation | Wang Q, et al. (2021) Constitutive Activity of Serotonin Receptor 6 Regulates Human Cerebral Organoids Formation and Depression-like Behaviors. Stem Cell Reports 16(1):75-88 |
| abstractText | 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. |
