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Int J Dev Neurosci. 2016 Apr;49:67-78. doi: 10.1016/j.ijdevneu.2015.11.006. Epub 2015 Nov 27.

Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model.

Author information

1
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.
2
Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
3
Department of Basic Medical Sciences, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.
4
Department of Pharmacology, Harbin Medical University in Daqing, Daqing, Heilongjiang 163319, China.
5
The Global Clinical and Translational Research Institute, Bethesda, MD 20814, USA.
6
The Global Clinical and Translational Research Institute, Bethesda, MD 20814, USA. Electronic address: zhangf28@gmail.com.
7
Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: wljhyd@ems.hrbmu.edu.cn.

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).

KEYWORDS:

Autism; Docosahexaenoic acid (DHA); Hippocampal cell; Learning impairment; Memory impairment; Neuroprotective

PMID:
26639559
DOI:
10.1016/j.ijdevneu.2015.11.006
[Indexed for MEDLINE]

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