ArticleFrontiers in cellular neuroscience2019
Social Stress-Induced Postsynaptic Hyporesponsiveness in Glutamatergic Synapses Is Mediated by PSD-Zip70-Rap2 Pathway and Relates to Anxiety-Like Behaviors.
Article in Frontiers in cellular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 8 citations in OpenAlex.
- Clinical Features, Mechanisms, and Management of Anxiety in Youth with Tic Disorders: A Narrative Review.Neuropsychiatric disease and treatment · 2026Review
- Stress-mediated dysregulation of the Rap1 small GTPase impairs hippocampal structure and function.iScience · 2023Article
- Article
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2 authors at 1 institution in 1 country.
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Abstract
PSD-Zip70 is a postsynaptic protein that regulates glutamatergic synapse formation and maturation by modulation of Rap2 activity. PSD-Zip70 knockout (PSD-Zip70KO) mice exhibit defective glutamatergic synaptic transmission in the prefrontal cortex (PFC) with aberrant Rap2 activation. As prefrontal dysfunction is implicated in the pathophysiology of stress-induced psychiatric diseases, we examined PSD-Zip70KO mice in a social defeat (SD) stress-induced mouse model of depression to investigate stress-induced alterations in synaptic function. Compared with wild-type (WT) mice, PSD-Zip70KO mice exhibited almost normal responses to SD stress in depression-related behaviors such as social activity, anhedonia, and depressive behavior. However, PSD-Zip70KO mice showed enhanced anxiety-like behavior irrespective of stress conditions. The density and size of dendritic spines of pyramidal neurons were reduced in the medial PFC (mPFC) in mice exposed to SD stress. Phosphorylation levels of the AMPA-type glutamate receptor (AMPA-R) GluA2 subunit at Ser880 were prominently elevated in mice exposed to SD stress, indicating internalization of surface-expressed AMPA-Rs and decreased postsynaptic responsiveness. Structural and functional impairments in postsynaptic responsiveness were associated with Rap2 GTPase activation in response to SD stress. Social stress-induced Rap2 activation was regulated by a PSD-Zip70-dependent pathway via interaction with SPAR/PDZ-GEF1. Notably, features such as Rap2 activation, dendritic spine shrinkage, and increased GluA2 phosphorylation were observed in the mPFC of PSD-Zip70KO mice even without SD stress. Together with our previous results, the present findings suggest that SD stress-induced postsynaptic hyporesponsiveness in glutamatergic synapses is mediated by PSD-Zip70-Rap2 signaling pathway and closely relates to anxiety-like behaviors.
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