{"corpus_id":251670303,"paper_sha":"bf105719dd9cf56633da3886e5d6cd790c3bc61b","doi":"10.1038/s42003-022-03813-y","arxiv_id":null,"pmid":35982261,"pmcid":"9388611","mag_id":null,"dblp_id":null,"acl_id":null,"title":"Adult re-expression of IRSp53 rescues NMDA receptor function and social behavior in IRSp53-mutant mice","year":2022,"publication_date":"2022-08-18","venue":"Communications Biology","journal":{"name":"Communications Biology","pages":null,"volume":"5"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":70,"citation_count":7,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"N-Methylaspartate","mj":true,"ui":"D016202"},{"d":"Nerve Tissue Proteins","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D009419"},{"d":"Receptors, N-Methyl-D-Aspartate","mj":true,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D016194"},{"d":"Signal Transduction","mj":false,"ui":"D015398"},{"d":"Social Behavior","mj":false,"ui":"D012919"},{"d":"Synaptic Transmission","mj":false,"ui":"D009435"}],"chemicals":[{"n":"Baiap2 protein, mouse","ui":"C539986","reg":"0"},{"n":"Nerve Tissue Proteins","ui":"D009419","reg":"0"},{"n":"Receptors, N-Methyl-D-Aspartate","ui":"D016194","reg":"0"},{"n":"N-Methylaspartate","ui":"D016202","reg":"6384-92-5"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://www.nature.com/articles/s42003-022-03813-y.pdf","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/bf105719dd9cf56633da3886e5d6cd790c3bc61b","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"IRSp53 (or BAIAP2) is an abundant excitatory postsynaptic scaffolding/adaptor protein that is involved in actin regulation and has been implicated in autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder. IRSp53 deletion in mice leads to enhanced NMDA receptor (NMDAR) function and social deficits that are responsive to NMDAR inhibition. However, it remains unclear whether IRSp53 re-expression in the adult IRSp53-mutant mouse brain after the completion of brain development could reverse these synaptic and behavioral dysfunctions. Here we employed a brain-blood barrier (BBB)-penetrant adeno-associated virus (AAV) known as PHP.eB to drive adult IRSp53 re-expression in IRSp53-mutant mice. The adult IRSp53 re-expression normalized social deficits without affecting hyperactivity or anxiety-like behavior. In addition, adult IRSp53 re-expression normalized NMDAR-mediated excitatory synaptic transmission in the medial prefrontal cortex. Our results suggest that adult IRSp53 re-expression can normalize synaptic and behavioral deficits in IRSp53-mutant mice and that BBB-penetrant adult gene re-expression has therapeutic potential. Re-expression of the insulin receptor substrate p53 (IRSp53) in adult IRSp53-mutant mice rescues behavioral and synaptic deficits, suggesting that adult re-expression may hold future therapeutic potential.","claims":[{"public_id":"cl_ce45c39bcc9cd022868aa687192115df","status":"active","text":"Adult IRSp53 re-expression did not affect hyperactivity or anxiety-like behavior.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_ce45c39bcc9cd022868aa687192115df"},{"public_id":"cl_81616bf607f9b564ccfbcd152a134dc6","status":"active","text":"Adult IRSp53 re-expression normalized NMDA receptor-mediated excitatory synaptic transmission in the medial prefrontal cortex.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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