{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xiao MF"],"funding":["NCATS NIH HHS","NIA NIH HHS","NIMH NIH HHS","NINDS NIH HHS","NCI NIH HHS"],"pagination":["eabf6935"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8612534"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["7(48)"],"pubmed_abstract":["Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contributi"],"journal":["Science advances"],"pubmed_title":["A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function."],"pmcid":["PMC8612534"],"funding_grant_id":["R35 NS097966","UL1 TR002345","P50 AG005681","R03 AG047999","K76 AG054863","UL1 TR000448","T32 CA193145","RF1 AG055974","R01 MH092443","P30 AG066444","P50 MH094268","KL2 TR000450","R01 MH105660","P01 AG026276","R01 NS081678","R01 MH107730"],"pubmed_authors":["Xiao MF","Craig MT","Lucey BP","Xu D","McBain CJ","Arnold DB","Sawa A","Zhou W","Jia M","Worley PF","Staley M","Chien CC","Reti IM","Pelkey KA","Conover Talbot C","Jiang C","Hayes LN","Savonenko A","Coughlin JM","Roh SE","Leweke FM","Zhou J"],"additional_accession":[]},"is_claimable":false,"name":"A biomarker-authenticated model of schizophrenia implicating NPTX2 loss of function.","description":"Schizophrenia is a polygenetic disorder whose clinical onset is often associated with behavioral stress. Here, we present a model of disease pathogenesis that builds on our observation that the synaptic immediate early gene NPTX2 is reduced in cerebrospinal fluid of individuals with recent onset schizophrenia. NPTX2 plays an essential role in maintaining excitatory homeostasis by adaptively enhancing circuit inhibition. NPTX2 function requires activity-dependent exocytosis and dynamic shedding at synapses and is coupled to circadian behavior. Behavior-linked NPTX2 trafficking is abolished by mutations that disrupt select activity-dependent plasticity mechanisms of excitatory neurons. Modeling NPTX2 loss of function results in failure of parvalbumin interneurons in their adaptive contributi","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2025-04-04T21:33:11.274Z","creation":"2022-02-11T13:27:17.507Z"},"accession":"S-EPMC8612534","cross_references":{"pubmed":["34818031"],"doi":["10.1126/sciadv.abf6935"]}}