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This study investigated the effect of docosahexaenoic acid (DHA) on hippocampal cell death, learning and memory alteration in an experimental rat autism model. We found that DHA supplementation (75, 150 or 300 mg\/kg\/day, 21 days) rescued the VPA (600 mg\/kg) induced DHA reduction in plasma and hippocampus in a dose\u2010dependent manner, increased the levels of hippocampal p\u2010CaMKII and p\u2010CREB without affecting total protein level, and altered BDNF\u2010AKT\u2010Bcl\u20102 signaling pathway, as well as inhibited the activity of caspase\u20103. DHA also influenced the content of malondialdehyde (MDA) and the activities of antioxidant enzymes in the VPA\u2010treated offspring. Consistent with the previous results, we also observed that 300 mg\/kg DHA supplementation markedly increased the cell survival, decreased the cell apoptosis, and increased mature neuronal cell in the hippocampus in VPA\u2010treated offspring. Utilizing the Morris water maze test, we found that DHA prevented cognitive impairment in offspring of VPA\u2010treated rats. The data suggested that DHA may play a neuroprotective role in hippocampal neuronal cell and ameliorates dysfunctions in learning and memory in this rat autism model. Thus, DHA could be used as treatment intervention for mitigating behavioral dysfunctions in autism spectrum disorder (ASD).<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2015.11.006","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T18:45:22Z","timestamp":1448649922000},"page":"67-78","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid\u2010induced rat autism model"],"prefix":"10.1002","volume":"49","author":[{"given":"Jingquan","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Health School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"},{"name":"Department of Nursing School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongli","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonggang","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Harbin Medical University in Daqing Daqing Heilongjiang 163319 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"The Global Clinical and Translational Research Institute Bethesda MD 20814 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Global Clinical and Translational Research Institute Bethesda MD 20814 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Health School of Public Health Harbin Medical University Harbin Heilongjiang 150081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91469-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2013.03.009"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"2013"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017397"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2004.09.006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.1996.tb01395.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-8624.1996.tb01830.x"},{"key":"e_1_2_7_9_1","unstructured":"CDC(2012)Prevalence of autism spectrum disorders\u2013Autism and Developmental Disabilities Monitoring Network 14 sites United States 2008. 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