biostudies-literatureShen WHHS | National Institutes of HealthNational Key R&D Program of ChinaLeona M. and Harry B. Helmsley Charitable TrustThe Engman FoundationMathers FoundationThe Open Project of State Key Laboratory of Membrane BiologyNIMH NIH HHSAnnette Merle-SmithBeijing municipal science & technology CommissionNational Natural Science Foundation of ChinaJPB Foundation4392-4399https://www.ebi.ac.uk/biostudies/studies/S-EPMC7049155biostudies-literatureUnknown117(8)The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By thProceedings of the National Academy of Sciences of the United States of AmericaSynaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice.PMC7049155U01 MH106882n/a2016YFA0101900Z18110000151800181771466U19MH1064342017-PG-MED001U19 MH1064343177148231830038Cao LXing ZWang QWYao JShi WLinker SWang HZhong YMi SSui SFLiu YNMarchetto MCGage FHZhao MYang YLu SYChen YLiu CGuo CKelsoe JRShen WAlda MfalseSynaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice.The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By th2020-01-01T00:00:00Z2020 Feb2025-04-22T10:35:04.217Z2025-04-05T23:37:05.398ZS-EPMC70491553204188210.1073/pnas.1918165117