{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:36:24Z","timestamp":1791448584539,"version":"4.3.3"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371460"],"award-info":[{"award-number":["82371460"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271487"],"award-info":[{"award-number":["82271487"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771404"],"award-info":[{"award-number":["81771404"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20201440"],"award-info":[{"award-number":["BK20201440"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,2]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n To explore the mechanism involved in variable phenotypes of epilepsy models induced by \u03b3\u2010aminobutyric acid type A \u03b32 subunit (\n GABRG2<\/jats:italic>\n ) mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The zebrafish carrying wild\u2010type (WT)\n GABRG2<\/jats:italic>\n , mutant\n GABRG2(P282S)<\/jats:italic>\n ,\n GABRG2(F343L)<\/jats:italic>\n and\n GABRG2(I107T)<\/jats:italic>\n were established by Tol2kit transgenesis system and Gateway method. Behavioral analysis of different transgenic zebrafish was performed with the DanioVision Video\u2010Track framework and the brain activity was analyzed by field potential recording with MD3000 Bio\u2010signal Acquisition and Processing System. The transcriptome analysis was applied to detect the underlying mechanisms of variable phenotypes caused by different\n GABRG2<\/jats:italic>\n mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The established Tg(\n hGABRG2<\/jats:italic>\n \n P282S<\/jats:italic>\n <\/jats:sup>\n ) zebrafish showed hyperactivity and spontaneous seizures, which were more sensitive to chemical and physical epileptic stimulations. Traditional antiepileptic drugs, such as Clonazepam (CBZ) and valproic acid (VPA), could ameliorate the hyperactivity in\n Tg(hGABRG2<\/jats:italic>\n \n P282S<\/jats:italic>\n <\/jats:sup>\n )<\/jats:italic>\n zebrafish. The metabolic pathway was significantly changed in the brain transcriptome of\n Tg(hGABRG2<\/jats:italic>\n \n P282S<\/jats:italic>\n <\/jats:sup>\n )<\/jats:italic>\n zebrafish. In addition, the behavioral activity, production of pro\u2010inflammatory factors, and activation of the IL\u20102 receptor signal pathway varied among the three mutant zebrafish lines.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n We successfully established transgenic zebrafish epileptic models expressing human mutant\n GABRG2(P282S)<\/jats:italic>\n , in which CBZ and VPA showed antiepileptic effects. Differential inflammatory responses, especially the SOCS\/JAK\/STAT signaling pathway, might be related to the phenotypes of genetic epilepsy induced by\n GABRG2<\/jats:italic>\n mutations. Further study will expand the pathological mechanisms of genetic epilepsies and provide a theoretical basis for searching for effective drug treatment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cns.14583","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T05:29:32Z","timestamp":1707974972000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Differential inflammation responses determine the variable phenotypes of epilepsy induced by\n \n GABRG2<\/i>\n <\/scp>\n mutations"],"prefix":"10.1111","volume":"30","author":[{"given":"Jiahui","family":"Sui","sequence":"first","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longwu","family":"Zhan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengtao","family":"Ji","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpeng","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maohong","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingding","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7599-6533","authenticated-orcid":false,"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Department of Neurology Affiliated Hospital of Nantong University, Medical School, Co\u2010innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179683"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000657"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.186999"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17336"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww272"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab338"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13785"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109802"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16670"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm-20-3745"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2004.11.031"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.107966"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X19666210826125341"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308208101"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2002.24501.x"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/11208340-000000000-00000"},{"issue":"2","key":"e_1_2_11_18_1","first-page":"CD013028","article-title":"Clonazepam monotherapy for treating people with newly diagnosed epilepsy (review)","author":"Brigo F","year":"2022","journal-title":"Cochrane Db Syst Rev"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-009-9013-5"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-016-0264-9"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-021-01050-4"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.05.030"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/479364"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s42494-020-00024-y"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0430-09.2009"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2015.11.002"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.178"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01250-3"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17023"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2008.07.018"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.01.017"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000042"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000343"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abc5763"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv182"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.05.063"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00651-8"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112365"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2023.111976"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0008-16.2016"}],"container-title":["CNS Neuroscience & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14583","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cns.14583","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.14583","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T14:21:12Z","timestamp":1771078872000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.14583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/cns.14583"],"URL":"https:\/\/doi.org\/10.1111\/cns.14583","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"2023-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e14583"}}