Maternal Docosahexaenoic Acid Feeding Protects Against Impairment of Learning and Memory and Oxidative Stress in Prenatally Stressed Rats: Possible Role of Neuronal Mitochondria Metabolism
Maternal Docosahexaenoic Acid Feeding Protects Against Impairment of Learning and Memory and Oxidative Stress in Prenatally Stressed Rats: Possible Role of Neuronal Mitochondria Metabolism
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DOI：
10.1089/ars.2010.3750
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发表时间：
2012-02-01
影响因子：
6.6
通讯作者：
Liu, Jiankang
中科院分区：
文献类型：
--
作者：
Feng, Zhihui;Zou, Xuan;Liu, Jiankang
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，没有研究已经进行了调查，产前应激诱导的行为和分子改变的后代的预防作用。在本研究中，大鼠在妊娠第14-20天暴露于束缚应激，每天3次，每次2小时;以100和300 mg/kg/天的剂量给予DHA，持续两周。结果如下：我们发现，产前束缚应激导致（1）学习和记忆障碍，（2）BDNF mRNA水平下降，（3）蛋白质氧化损伤，（4）一氧化氮合酶表达增强和细胞凋亡，（5）线粒体代谢异常，包括线粒体复合物I-V的变化，以及参与线粒体融合/分裂的蛋白质表达增强（Mfn-1、Mfn-2、Drp-1）和自噬（Atg 3、Atg 7、Beclin-1、p-Akt和p-m TOR）。创新：除了在儿童大脑发育中的众所周知的作用外，我们还报道了DHA在保护产前应激诱导的认知功能障碍方面的新发现，涉及线粒体功能和动力学的调节。结论：母亲喂养DHA可显著预防产前应激诱导的学习和记忆障碍，并使雄性和雌性后代海马体中的氧化损伤、细胞凋亡和线粒体代谢生物标志物正常化。这些结果表明，母亲喂养DHA对产前应激诱导的脑功能障碍具有预防作用，线粒体代谢的调节可能在DHA保护中起关键作用。抗氧化剂。氧化还原信号。16，275-289。
Aims: Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in postnatal brain development. However, no study has been performed to investigate its preventive effect on prenatal stress-induced behavioral and molecular alterations in offspring. In the present study, rats were exposed to restraint stress on days 14-20 of pregnancy, three times a day, 2 hours each time; DHA was given at the doses of 100 and 300 mg/kg/day for two weeks. Results: We showed that prenatal restraint stress caused (1) learning and memory impairment, (2) BDNF mRNA level decrease, (3) oxidative damage to proteins, (4) enhanced expression of nitric oxide synthase and apoptosis, and (5) abnormalities in mitochondrial metabolism that included changes in mitochondrial complexes I-V, and enhancement of expression of proteins involved in mitochondrial fusion/fission (Mfn-1, Mfn-2, Drp-1) and autophagy (Atg3, Atg7, Beclin-1, p-Akt, and p-m TOR) in the hippocampus of offspring. Innovation: Besides the well-known role in child brain development, we reported the novel finding of DHA in protecting prenatal stress-induced cognitive dysfunction involving the modulation of mitochondrial function and dynamics. Conclusion: Maternal feeding of DHA significantly prevented prenatal stress-induced impairment of learning and memory and normalized the biomarkers of oxidative damage, apoptosis, and mitochondrial metabolism in the hippocampus of both male and female offspring. These results suggest that maternal feeding of DHA exerts preventive effects on prenatal stress-induced brain dysfunction and that modulation of mitochondrial metabolism may play critical role in DHA protection. Antioxid. Redox Signal. 16, 275-289.