{"doi":"10.1093/cercor/bhy254","title":"CAPON Is a Critical Protein in Synaptic Molecular Networks in the Prefrontal Cortex of Mood Disorder Patients and Contributes to Depression-Like Behavior in a Mouse Model","abstract":"<jats:title>Abstract</jats:title><jats:p>Aberrant regulation and activity of synaptic proteins may cause synaptic pathology in the prefrontal cortex (PFC) of mood disorder patients. Carboxy-terminal PDZ ligand of NOS1 (CAPON) is a critical scaffold protein linked to synaptic proteins like nitric oxide synthase 1, synapsins. We hypothesized that CAPON is altered together with its interacting synaptic proteins in the PFC in mood disorder patients and may contribute to depression-like behaviors in mice subjected to chronic unpredictable mild stress (CUMS). Here, we found that CAPON-immunoreactivity (ir) was significantly increased in the dorsolateral PFC (DLPFC) and anterior cingulate cortex in major depressive disorder (MDD), which was accompanied by an upregulation of spinophilin-ir and a downregulation of synapsin-ir. The increases in CAPON and spinophilin and the decrease in synapsin in the DLPFC of MDD patients were also seen in the PFC of CUMS mice. CAPON-ir positively correlated with spinophilin-ir (but not with synapsin-ir) in mood disorder patients. CAPON colocalized with spinophilin in the DLPFC of MDD patients and interacted with spinophilin in human brain. Viral-mediated CAPON downregulation in the medial PFC notably reversed the depression-like behaviors in the CUMS mice. These data suggest that CAPON may contribute to aspects of depressive behavior, possibly as an interacting protein for spinophilin in the PFC.</jats:p>","journal":"Cerebral Cortex","year":2019,"id":633939,"datarank":0.47032413238937254,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.0,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":486367,"name":"Tong Zhang","orcid":"0000-0002-5511-2558","position":1,"is_corresponding":false},{"id":12970,"name":"Lei Jin","orcid":"0000-0002-7264-4409","position":2,"is_corresponding":false},{"id":374823,"name":"Dong Liang","orcid":"0000-0001-6632-8066","position":3,"is_corresponding":false},{"id":195847,"name":"Guangwei Fan","orcid":null,"position":4,"is_corresponding":false},{"id":1643850,"name":"Yunnong Song","orcid":null,"position":5,"is_corresponding":false},{"id":1643851,"name":"Paul J Lucassen","orcid":null,"position":6,"is_corresponding":false},{"id":1643852,"name":"Rutong Yu","orcid":null,"position":7,"is_corresponding":false},{"id":1643854,"name":"Dick F Swaab","orcid":null,"position":8,"is_corresponding":false},{"id":1643849,"name":"Shangfeng Gao","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"CAPON Is a Critical Protein in Synaptic Molecular Networks in the Prefrontal Cortex of Mood Disorder Patients and Contributes to Depression-Like Behavior in a Mouse Model","abstract":"<jats:title>Abstract</jats:title><jats:p>Aberrant regulation and activity of synaptic proteins may cause synaptic pathology in the prefrontal cortex (PFC) of mood disorder patients. Carboxy-terminal PDZ ligand of NOS1 (CAPON) is a critical scaffold protein linked to synaptic proteins like nitric oxide synthase 1, synapsins. We hypothesized that CAPON is altered together with its interacting synaptic proteins in the PFC in mood disorder patients and may contribute to depression-like behaviors in mice subjected to chronic unpredictable mild stress (CUMS). Here, we found that CAPON-immunoreactivity (ir) was significantly increased in the dorsolateral PFC (DLPFC) and anterior cingulate cortex in major depressive disorder (MDD), which was accompanied by an upregulation of spinophilin-ir and a downregulation of synapsin-ir. The increases in CAPON and spinophilin and the decrease in synapsin in the DLPFC of MDD patients were also seen in the PFC of CUMS mice. CAPON-ir positively correlated with spinophilin-ir (but not with synapsin-ir) in mood disorder patients. CAPON colocalized with spinophilin in the DLPFC of MDD patients and interacted with spinophilin in human brain. Viral-mediated CAPON downregulation in the medial PFC notably reversed the depression-like behaviors in the CUMS mice. These data suggest that CAPON may contribute to aspects of depressive behavior, possibly as an interacting protein for spinophilin in the PFC.</jats:p>","is_dataset_classified":null,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30307500","pmcid":null,"openalex_id":"https://openalex.org/W2897312845","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"31400930","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81472345","title":null},{"funder_name":"Natural Science Foundation of Jiangsu Province","grant_id":"BK20140217","title":null},{"funder_name":"Key Research & Development Plan of Jiangsu Province","grant_id":"BE2016646","title":null},{"funder_name":"China Postdoctoral Science Foundation","grant_id":"2015M570480","title":null},{"funder_name":"China Postdoctoral Science Foundation","grant_id":"2016T90505","title":null},{"funder_name":"Jiangsu Overseas Research & Training Program for University Prominent Young & Middle-aged Teachers, and Jiangsu Provincial Medical Youth Talent","grant_id":"QNRC2016787","title":null},{"funder_name":"Jiangsu Provincial Qing Lan Project","grant_id":"","title":null}],"total_grants":8,"fwci":0.6744,"citation_percentile":0.62125325,"influential_citations":0,"citation_trend":[{"year":2019,"count":3},{"year":2021,"count":4},{"year":2022,"count":2},{"year":2023,"count":6},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://handle.uba.uva.nl/personal/pure/en/publications/capon-is-a-critical-protein-in-synaptic-molecular-networks-in-the-prefrontal-cortex-of-mood-disorder-patients-and-contributes-to-depressionlike-behavior-in-a-mouse-model(95caf8c7-a365-49de-89f3-652b56c1072f).html","host_type":"repository"},{"url":"https://handle.uba.uva.nl/personal/pure/en/publications/capon-is-a-critical-protein-in-synaptic-molecular-networks-in-the-prefrontal-cortex-of-mood-disorder-patients-and-contributes-to-depressionlike-behavior-in-a-mouse-model(95caf8c7-a365-49de-89f3-652b56c1072f).html","host_type":"repository"},{"url":"http://academic.oup.com/cercor/article-pdf/29/9/3752/29104669/bhy254.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/cercor/bhy254","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30307500","host_type":"repository"},{"url":"https://pure.knaw.nl/portal/en/publications/b4fb91ea-fe8a-4a8f-a8e8-298273a94faf","host_type":"repository"},{"url":"https://hdl.handle.net/11245.1/95caf8c7-a365-49de-89f3-652b56c1072f","host_type":"repository"},{"url":"https://hdl.handle.net/20.500.11755/b4fb91ea-fe8a-4a8f-a8e8-298273a94faf","host_type":"repository"},{"url":"https://dare.uva.nl/personal/pure/en/publications/capon-is-a-critical-protein-in-synaptic-molecular-networks-in-the-prefrontal-cortex-of-mood-disorder-patients-and-contributes-to-depressionlike-behavior-in-a-mouse-model(95caf8c7-a365-49de-89f3-652b56c1072f).html","host_type":"repository"}],"fields_of_study":["Neuroscience and Neuropharmacology Research","Tryptophan and brain disorders","Stress Responses and Cortisol","Adaptor Proteins, Signal Transducing","Animals","Brain","Depression","Major Depressive Disorder","Disease Models, Animal","Gyrus Cinguli","Humans","Microfilament Proteins","Nerve Tissue Proteins","Neurons","Prefrontal Cortex","Synapses","Synapsins","Neurabins"],"mesh_terms":["Neurabins","Animals","Brain","Depression","Depressive Disorder, Major","Major Depressive Disorder","Disease Models, Animal","Gyrus Cinguli","Humans","Microfilament Proteins","Nerve Tissue Proteins","Neurons","Synapses","Synapsins","Prefrontal Cortex","Adaptor Proteins, Signal Transducing"],"keywords":["Capon","Synapsin I","Synapsin","Prefrontal cortex","Neuroscience","Anterior cingulate cortex","Major depressive disorder","Downregulation and upregulation","Dorsolateral prefrontal cortex","Biology","Psychology","Synaptic vesicle","Amygdala","Biochemistry","Cognition","Computer science","Stress","Spinophilin","Major Depression","Nos1ap"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T12:54:26.047436Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}