ArticleEMBO reports2022
CIP2A deficiency promotes depression-like behaviors in mice through inhibition of dendritic arborization.
Article in EMBO reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 7 citations in OpenAlex.
- Mouse neuronal dendritic complexity and resilience to stress-induced depression in Drosophila melanogaster are enhanced by Withania somnifera alkaloids.Journal of ethnopharmacology · 2026Article
- Mechanism of N6-Methyladenosine Modification in the Pathogenesis of Depression.Molecular neurobiology · 2025Review
- CIP2A promotes bronchiolitis obliterans by activating the NF‑κB pathway.Molecular medicine reports · 2025Article
- Tau induces inflammasome activation and microgliosis through acetylating NLRP3.Clinical and translational medicine · 2024Article
- CIP2A deficiency promotes depression-like behaviors in mice through inhibition of dendritic arborization.EMBO reports · 2022Article
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depressive disorder (MDD) is a severe mental illness. Decreased brain plasticity and dendritic fields have been consistently found in MDD patients and animal models; however, the underlying molecular mechanisms remain to be clarified. Here, we demonstrate that the deletion of cancerous inhibitor of PP2A (CIP2A), an endogenous inhibitor of protein phosphatase 2A (PP2A), leads to depression-like behaviors in mice. Hippocampal RNA sequencing analysis of CIP2A knockout mice shows alterations in the PI3K-AKT pathway and central nervous system development. In primary neurons, CIP2A stimulates AKT activity and promotes dendritic development. Further analysis reveals that the effect of CIP2A in promoting dendritic development is dependent on PP2A-AKT signaling. In vivo, CIP2A deficiency-induced depression-like behaviors and impaired dendritic arborization are rescued by AKT activation. Decreased CIP2A expression and impaired dendrite branching are observed in a mouse model of chronic unpredictable mild stress (CUMS). Indicative of clinical relevance to humans, CIP2A expression is found decreased in transcriptomes from MDD patients. In conclusion, we discover a novel mechanism that CIP2A deficiency promotes depression through the regulation of PP2A-AKT signaling and dendritic arborization.
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