title: Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model.
abstract: Prenatal exposure to valproic acid (VPA) in rat offspring is capable of inducing experimental autism with neurobehavioral aberrations. 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-dependent manner, increased the levels of hippocampal p-CaMKII and p-CREB without affecting total protein level, and altered BDNF-AKT-Bcl-2 signaling pathway, as well as inhibited the activity of caspase-3. DHA also influenced the content of malondialdehyde (MDA) and the activities of antioxidant enzymes in the VPA-treated 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-treated offspring. Utilizing the Morris water maze test, we found that DHA prevented cognitive impairment in offspring of VPA-treated 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).
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China; Department of Nursing, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Jingquan
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Xuelai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Basic Medical Sciences, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Basic Medical Sciences, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Harbin Medical University in Daqing, Daqing, Heilongjiang 163319, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Global Clinical and Translational Research Institute, Bethesda, MD 20814, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: The Global Clinical and Translational Research Institute, Bethesda, MD 20814, USA. Electronic address: zhangf28@gmail.com.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: wljhyd@ems.hrbmu.edu.cn.
authors.forename: Lijie
authors.initials: L
authors.lastname: Wu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity; D001321:Autistic Disorder / Q000139:chemically induced* / Q000150:complications; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000627:therapeutic use*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014635:Valproic Acid / Q000633:toxicity
chemical_list: D000927:Anticonvulsants; D018696:Neuroprotective Agents; D004281:Docosahexaenoic Acids; D008315:Malondialdehyde; D014635:Valproic Acid; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase
keywords: Autism; Docosahexaenoic acid (DHA); Hippocampal cell; Learning impairment; Memory impairment; Neuroprotective