{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:38:26Z","timestamp":1786700306518,"version":"build-2736575974"},"reference-count":94,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Central Nervous System Drug Key Laboratory of Sichuan Province","award":["200029-01SZ"],"award-info":[{"award-number":["200029-01SZ"]}]},{"name":"Youth Project of Affiliated Hospital of Southwest Medical University","award":["2024LCYXZX64"],"award-info":[{"award-number":["2024LCYXZX64"]}]},{"name":"Youth Project of Southwest Medical University","award":["2021ZKQN064"],"award-info":[{"award-number":["2021ZKQN064"]}]},{"name":"high-quality development project of Zigong City Hospital","award":["ZG-KY-2023-047, ZG-PT-2023-026"],"award-info":[{"award-number":["ZG-KY-2023-047, ZG-PT-2023-026"]}]},{"name":"Zigong Science and Technology Bureau","award":["2024-NKY-01-05"],"award-info":[{"award-number":["2024-NKY-01-05"]}]},{"name":"Zigong Science and Technology Bureau","award":["2022ZCNKY02"],"award-info":[{"award-number":["2022ZCNKY02"]}]},{"name":"Zigong Science and Technology Bureau","award":["2021YXY03"],"award-info":[{"award-number":["2021YXY03"]}]},{"DOI":"10.13039\/501100019971","name":"Luzhou Science and Technology Bureau","doi-asserted-by":"publisher","award":["2022-SYF-96"],"award-info":[{"award-number":["2022-SYF-96"]}],"id":[{"id":"10.13039\/501100019971","id-type":"DOI","asserted-by":"publisher"}]},{"name":"STI2030-Major Project","award":["2021ZD0201103"],"award-info":[{"award-number":["2021ZD0201103"]}]},{"DOI":"10.13039\/501100004829","name":"Sichuan Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2022YFS0615"],"award-info":[{"award-number":["2022YFS0615"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Sichuan Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["2023NSFSC0124"],"award-info":[{"award-number":["2023NSFSC0124"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Social withdrawal is a core symptom of schizophrenia (SCZ), yet its underlying molecular mechanisms remain unclear. G\u03b113 (GNA13), a G protein alpha subunit, has been implicated in SCZ susceptibility. This study investigated the role of G\u03b113 in social behavior by overexpressing it in the medial prefrontal cortex (mPFC) pyramidal neurons of mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>In this study, we first constructed CRE recombinase overexpressing G\u03b113 gene mice using CRISPR\/Cas9 technology, tested the social behaviors by three-box socialization test, detected the changes of neuronal activities during social activities in mice by calcium signal fiber-optic recordings, observed the changes of dendritic spines by Golgi staining, applied RNA sequencing (RNA-Seq) to find the relevant targets, and observed whether it could reverse the abnormalities by pharmacological experiments social behavior. The electrophysiological characteristics of G\u03b113 overexpression were investigated using the whole-cell membrane clamp technique, followed by assessment of the severity of SCZ patients and social withdrawal using the PANSS scale and measurement of human plasma G\u03b113 protein levels using the ELISA technique, and the clinical correlation between the two was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Results<\/jats:title>\n                    <jats:p>G\u03b113 overexpression (G\u03b113-OE) mice exhibited significant social deficits in the three-chamber test, showing reduced sociability but normal social novelty recognition. Fiber photometry recordings revealed decreased neuronal activity during social interactions, and Golgi staining showed reduced dendritic spine density in mPFC pyramidal neurons. RNA-Seq identified downregulation of Adcyap1, affecting the cAMP\/PKA signaling pathway and NMDA receptor (NMDAR) function. Pharmacological activation of Adcyap1 with PACAP-38 or NMDAR with D-cycloserine rescued the social deficits and restored synaptic function. Conversely, knockdown of G\u03b113 in an MK-801-induced SCZ mouse model ameliorated social behavior abnormalities. Clinically, patients with SCZ exhibited elevated plasma levels of G\u03b113, which positively correlated with the severity of social withdrawal symptoms measured by the PANSS G16 item.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that overexpression of G\u03b113 in the mPFC impairs social behavior by disrupting neuronal function and synaptic plasticity via the Adcyap1\/cAMP\/PKA\/NMDAR pathway. Targeting G\u03b113 may offer a novel therapeutic strategy for addressing social deficits in SCZ.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/schbul\/sbaf131","type":"journal-article","created":{"date-parts":[[2025,7,14]],"date-time":"2025-07-14T14:06:59Z","timestamp":1752502019000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>G\u03b113<\/i>\n                    Overexpression in the Medial Prefrontal Cortex Disrupts Social Behavior Through the Adcyap1\/cAMP\/PKA\/NMDAR Pathway"],"prefix":"10.1093","volume":"52","author":[{"given":"Rui","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]},{"name":"Mental Health Research Center, Zigong Affiliated Hospital of Southwest Medical University & Zigong Institute of Brain Science , Gongshu road 2-666, Gongjing district, Zigong, 643000, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]},{"name":"Mental Health Research Center, Zigong Affiliated Hospital of Southwest Medical University & Zigong Institute of Brain Science , Gongshu road 2-666, Gongjing district, Zigong, 643000, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglan","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binglong","family":"Wang","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Zigong Affiliated Hospital of Southwest Medical University & Zigong Institute of Brain Science , Gongshu road 2-666, Gongjing district, Zigong, 643000, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfei","family":"Wu","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Zigong Affiliated Hospital of Southwest Medical University & Zigong Institute of Brain Science , Gongshu road 2-666, Gongjing district, Zigong, 643000, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kezhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, Luzhou, Sichuan , 646000,","place":["China"]},{"name":"Mental Health Research Center, Zigong Affiliated Hospital of Southwest Medical University & Zigong Institute of Brain Science , Gongshu road 2-666, Gongjing district, Zigong, 643000, Sichuan ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-0439","authenticated-orcid":false,"given":"Kenji","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health , Chiba , 260-8670,","place":["Japan"]},{"name":"Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University , Luzhou, Sichuan , 646000,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8341-2286","authenticated-orcid":false,"given":"Bo","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders Key Laboratory of Luzhou, Institute of Cardiovascular Research, The Affiliated Hospital, Southwest Medical University , Taiping Street 25, Jiangyang district, 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