Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model
Neuroprotective effects of docosahexaenoic acid on hippocampal cell death and learning and memory impairments in a valproic acid-induced rat autism model
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二十二碳六烯酸对丙戊酸诱导的大鼠自闭症模型中海马细胞死亡以及学习记忆障碍的神经保护作用
DOI：
10.1016/j.ijdevneu.2015.11.006
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发表时间：
2016-04-01
影响因子：
1.8
通讯作者：
Wu, Lijie
中科院分区：
文献类型：
--
作者：
Gao, Jingquan;Wang, Xuelai;Wu, Lijie
产前暴露于丙戊酸（VPA）的大鼠后代能够诱导实验性自闭症与神经行为畸变。本研究探讨了二十二碳六烯酸（DHA）对实验性孤独症大鼠模型海马细胞死亡、学习记忆改变的影响。我们发现，DHA补充（75、150或300 mg/kg/天，21天）以剂量依赖性方式挽救了VPA（600 mg/kg）诱导的血浆和海马中DHA减少，增加了海马p-CaMKII和p-CREB的水平，而不影响总蛋白水平，改变了BDNF-AKT-Bcl-2信号通路，并抑制了caspase-3的活性。DHA还影响VPA处理后代体内丙二醛（MDA）含量和抗氧化酶活性。与先前的结果一致，我们还观察到300 mg/kg DHA补充剂显著增加VPA处理后代海马中的细胞存活，减少细胞凋亡，并增加成熟神经元细胞。利用Morris水迷宫测试，我们发现DHA预防VPA处理大鼠后代的认知障碍。提示DHA对孤独症大鼠海马神经元具有神经保护作用，可改善孤独症大鼠的学习记忆功能障碍。因此，DHA可以用作治疗干预，以减轻自闭症谱系障碍（ASD）的行为功能障碍。(C)2016由Elsevier Ltd.代表ISDN出版。
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). (C) 2016 Published by Elsevier Ltd. on behalf of ISDN.