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Insulin hypoactivity caused by Synaptotagmin-7 deficits contributes to depression-like behaviors and diurnal behavioral fluctuation

ABSTRACT: Synaptotagmin-7 (Syt7) KO mice show diurnal fluctuations of mania- and depression-like behavioral abnormalities. Although GluN2B-NMDAR hypoactivity has been shown to be involved in the induction of mania-like behaviors of the Syt7 KO mice in the dark phase, the reasons for the depression-like behaviors in the light phase and behavioral fluctuation remain unknown. Here, we show that bipolar I disorder (BDI) patient induced pluripotent stem cell (iPSC)-derived islet-like organoids exhibited Syt7-dependent insulin secretion defects; moreover, Syt7 deficiency-induced insulin hyposecretion generated depression-like behaviors in Syt7 KO mice in the light phase. Furthermore, pancreatic insulin secretion and neuronal activity showed opposite diurnal patterns, in which the Syt7 deficiency-induced disequilibrium induced periodic antagonistic shifts in the mania- and depression-like behaviors. Finally, using RNA-seq analysis, we explored downstream pathways that might underlie the diurnal fluctuation of behaviors. Therefore, Syt7 deficiency-induced insulin hypoactivity contributed to light-phase depression-like behaviors and diurnal behavioral fluctuations in the mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE282863 | GEO | 2025/05/14

REPOSITORIES: GEO

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Insulin hypoactivity caused by Synaptotagmin-7 deficits contributes to depression-like behaviors and diurnal behavioral fluctuation

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