Ppp4r3a deficiency leads to depression-like behaviors in mice by modulating the synthesis of synaptic proteins.

ABSTRACT: Chronic stress is one of the main risk factors for the onset of major depressive disorder. Chronic unpredictable mild stress results in reduced expression of synaptic proteins and depression-like behaviors in rodent models. However, the upstream molecule that senses the demand for synaptic proteins and initiates their synthesis under chronic stress remains unknown. In this study, chronic unpredictable mild stress reduced the expression of PPP4R3A in the prefrontal cortex and hippocampus in mice. Selective knockout of Ppp4r3a in the cortex and hippocampus mimicked the depression- and anxiety-like behavioral effects of chronic stress in mice. Notably, Ppp4r3a deficiency led to downregulated mTORC1 signaling, which resulted in reduced synthesis of synaptic proteins and impaired synaptic funct

SUBMITTER: Gao F 

PROVIDER: S-EPMC9150120 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature