ArticleDisease models & mechanisms2022
Ppp4r3a deficiency leads to depression-like behaviors in mice by modulating the synthesis of synaptic proteins.
Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 6 citations in OpenAlex.
- TPM-like manipulations exerted an antidepressant effect and regulated amino acid metabolism and GHR/IGF-1 pathway in the liver in adolescent female CUMS rats.Frontiers in physiology · 2026Article
- The Role of S6K1 in Aging and Alzheimer's Disease: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Untargeted Metabolomics Revealed that Quercetin Inhibited Ferroptosis by Improving Metabolic Disorder in the Hippocampus of Perimenopausal Depression Model Rats.Molecular neurobiology · 2025Article
- Near-infrared light induces neurogenesis and modulates anxiety-like behavior.Stem cell research & therapy · 2024Article
- SMEK1 ablation promotes glucose uptake and improves obesity-related metabolic dysfunction via AMPK signaling pathway.American journal of physiology. Endocrinology and metabolism · 2024Article
- Revealing genetic causality between blood-based biomarkers and major depression in east Asian ancestry.Frontiers in psychiatry · 2024Article
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Authors and funding
13 authors at 1 institution in 1 country.
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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 functions. By contrast, overexpression of Ppp4r3a in the cortex and hippocampus protected against behavioral and synaptic deficits induced by chronic stress in a PPP4R3A-mTORC1-dependent manner. Rapamycin treatment of Ppp4r3a-overexpressing neurons blocked the regulatory effect of Ppp4r3a on the synthesis of synaptic proteins by directly inhibiting mTORC1. Overall, our results reveal a regulatory role of Ppp4r3a in driving synaptic protein synthesis in chronic stress.
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