{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:46:08Z","timestamp":1787496368483,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Fujian Province, China","award":["2022J011404"],"award-info":[{"award-number":["2022J011404"]}]},{"name":"Natural Science Foundation of Fujian Province, China","award":["2024J011397"],"award-info":[{"award-number":["2024J011397"]}]},{"name":"Natural Science Foundation of Xiamen, China","award":["3502Z20227076"],"award-info":[{"award-number":["3502Z20227076"]}]},{"name":"Natural Science Foundation of Xiamen, China","award":["3502Z202573080"],"award-info":[{"award-number":["3502Z202573080"]}]},{"name":"Natural Science Foundation of Xiamen Medical College, China","award":["K2022-04"],"award-info":[{"award-number":["K2022-04"]}]},{"name":"Natural Science Foundation of Xiamen Medical College, China","award":["K2022-10"],"award-info":[{"award-number":["K2022-10"]}]},{"name":"Joint Funds for the Innovation of Science and Technology of Fujian Province","award":["2024Y9693"],"award-info":[{"award-number":["2024Y9693"]}]},{"name":"Scientific and Technological Plan Projects of Xiamen","award":["3502Z20224ZD1298"],"award-info":[{"award-number":["3502Z20224ZD1298"]}]},{"name":"Scientific and Technological Plan Projects of Xiamen","award":["3502Z20244ZD1146"],"award-info":[{"award-number":["3502Z20244ZD1146"]}]},{"name":"Fujian Provincial College Students Innovation and Entrepreneurship Training Program","award":["202412631009"],"award-info":[{"award-number":["202412631009"]}]},{"name":"Fujian Provincial College Students Innovation and Entrepreneurship Training Program","award":["202412631012"],"award-info":[{"award-number":["202412631012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social communication and repetitive behaviors, involving various brain regions. Emerging evidence highlights the critical role of the cerebellum in the pathophysiology of autism; however, the underlying molecular mechanisms remain poorly understood. This study aimed to establish a prenatal valproic acid (VPA)-induced mouse model of ASD and explore the potential molecular mechanisms underlying cerebellar ASD-like phenotypes through DIA-based proteomics and bioinformatics analyses. Significant cognitive impairment and anxiety-like behaviors were detected using an open field test and novel object test following VPA exposure, respectively. Additionally, reduced numbers of Purkinje cells with irregular arrangement were observed in the cerebellum. Furthermore, cerebellar proteomics analyses revealed that they identified 193 differentially expressed proteins (DEPs) involved in multiple pathways, including axon guidance, glutamatergic synapse, long-term potentiation, and calcium signaling, among others. Notably, dysfunction of glutamate receptor signaling and disruptions in axon-guidance signaling appear to be major molecular mechanisms underlying cerebellar impairment. Together, these findings suggest that Grin2b may serve as a critical molecule linking synaptic neurotransmission and neurodevelopmental disorders. Thus, Grin2b may represent a potential therapeutic target for addressing cognitive impairment in ASD.<\/jats:p>","DOI":"10.3390\/toxics13100833","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T14:16:29Z","timestamp":1759241789000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cerebellar Mechanisms Underlying Autism-like Cognitive Deficits in Mouse Offspring with Prenatal Valproic Acid Exposure"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3984-5970","authenticated-orcid":false,"given":"Juan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3463-1050","authenticated-orcid":false,"given":"Xu-Lan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Han","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Wei","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Hui","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Su","sequence":"additional","affiliation":[{"name":"School of Public Health, Fujian Medical University, Fuzhou 350122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8806-2621","authenticated-orcid":false,"given":"Xiao-Chun","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1186\/s12888-024-05643-0","article-title":"Prenatal, perinatal and parental risk factors for autism spectrum disorder in China: A case- control study","volume":"24","author":"Yuan","year":"2024","journal-title":"BMC Psychiatry"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1001\/jamapsychiatry.2023.4347","article-title":"Neighborhood Disadvantage and Autism Spectrum Disorder in a Population With Health Insurance","volume":"81","author":"Yu","year":"2024","journal-title":"JAMA Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13229-020-00342-5","article-title":"Prevalence and cumulative incidence of autism spectrum disorders and the patterns of co-occurring neurodevelopmental disorders in a total population sample of 5-year-old children","volume":"11","author":"Saito","year":"2020","journal-title":"Mol. 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