Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid
Maternal DHA supplementation protects rat offspring against impairment of learning and memory following prenatal exposure to valproic acid
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母体 DHA 补充剂可保护大鼠后代在产前接触丙戊酸后免受学习和记忆障碍
DOI：
10.1016/j.jnutbio.2016.07.003
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发表时间：
2016-09-01
影响因子：
5.6
通讯作者：
Wu, Lijie
中科院分区：
文献类型：
--
作者：
Gao, Jingquan;Wu, Hongmei;Wu, Lijie
二十二碳六烯酸（22：6 n-3; DHA）在出生后的大脑发育中起着关键作用。然而，还没有研究调查DHA对产前丙戊酸（VPA）诱导的后代行为和分子改变的预防作用。本研究旨在评价孕期暴露于丙戊酸的大鼠通过母体喂养DHA对子代的神经保护作用。在本研究中，大鼠在妊娠第12.5天暴露于VPA;从妊娠第1天至第21天，以100、300和500 mg/kg/天的剂量给予DHA，持续3周。结果表明，母亲给产前暴露于VPA的小鼠喂食DHA（1）可预防VPA诱导的学习和记忆障碍，但不改变社会相关行为，（2）增加子代血浆和海马中的总DHA含量，（3）挽救VPA诱导的海马CA 1区神经元丢失和锥体细胞凋亡，（4）影响海马组织中丙二醛、谷胱甘肽的含量及超氧化物歧化酶、谷胱甘肽的活性;（5）改变海马组织中凋亡相关蛋白的水平（6）增加海马中p-CaMK Ⅱ和p-CREB蛋白的相对水平。这些发现表明，母亲喂养DHA可以预防产前VPA诱导的学习和记忆障碍，使后代海马中与氧化应激和凋亡相关的几种不同分子正常化，并对产前WA诱导的脑功能障碍发挥预防作用。(C)2016 Elsevier Inc. All rights reserved.
Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, there have been no studies investigating the preventive effect of DHA on prenatal valproic acid (VPA)-induced behavioral and molecular alterations in offspring. The present study was to evaluate the neuroprotective effects in offspring using maternal feeding of DHA to rats exposed to VPA in pregnancy. In the present study, rats were exposed to VPA on day 12.5 of pregnancy; DHA was administered at the dosages of 100, 300 and 500 mg/kg/day for 3 weeks from day 1 to 21 of pregnancy. The results showed that maternal feeding of DHA to the prenatal exposed to VPA (1) prevented VPA-induced learning and memory impairment but did not change social-related behavior, (2) increased total DHA content in offspring plasma and hippocampus, (3) rescued VPA-induced neuronal loss and apoptosis of pyramidal cells in hippocampal CA1, (4) influenced the content of malondialdehyde and glutathione and the activities of superoxide dismutase and glutathione in the hippocampus, (5) altered levels of apoptosis-related proteins (Bcl-2, Bax and caspase-3) and inhibited the activity of caspase-3 in offspring hippocampus and (6) enhanced relative levels of p-CaMKII and p-CREB proteins in the hippocampus. These findings suggest that maternal feeding with DHA may prevent prenatal VPA-induced impairment of learning and memory, normalize several different molecules associated with oxidative stress and apoptosis in the hippocampus of offspring, and exert preventive effects on prenatal WA -induced brain dysfunction. (C) 2016 Elsevier Inc. All rights reserved.