Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid.
Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid.
复制标题
DOI：
10.1038/s41598-017-06630-0
复制
发表时间：
2017-07-24
影响因子：
4.6
通讯作者：
Yamazaki T
中科院分区：
文献类型：
--
作者：
Ishihara Y;Itoh K;Tanaka M;Tsuji M;Kawamoto T;Kawato S;Vogel CFA;Yamazaki T
一些研究表明二十二碳六烯酸（DHA）可以减轻癫痫发作；然而，它实现这种效果的分子机制在很大程度上仍然是未知的。DHA刺激类视黄醇X受体，据报道，该受体调节细胞色素P450芳香化酶（P450arom）的表达。本研究旨在阐明DHA如何抑制癫痫发作，重点关注大脑中17β-雌二醇合成的调节。膳食中添加DHA不仅增加了P450arom的表达，还增加了大脑皮层中17β-雌二醇的表达。DHA对戊四唑引起的癫痫发作的持续时间和评分没有影响，但明显延长了癫痫发作的潜伏期。P450arom抑制剂来曲唑可降低17β-雌二醇水平，并完全抑制DHA引起的癫痫发作潜伏期延长。这些结果表明，DHA通过促进大脑中17β-雌二醇的合成来延缓癫痫发作。DHA上调大脑皮层抗氧化酶的表达。DHA能明显减弱戊四唑对大脑皮层的氧化作用，来曲唑能完全抑制这种抑制作用。因此，17β-雌二醇的抗氧化作用可能参与了DHA介导的癫痫发作的预防。本研究揭示了脑内17β-雌二醇介导DHA的生理作用。
Several studies have shown that docosahexaenoic acid (DHA) attenuates epileptic seizures; however, the molecular mechanism by which it achieves this effect is still largely unknown. DHA stimulates the retinoid X receptor, which reportedly regulates the expression of cytochrome P450 aromatase (P450arom). This study aimed to clarify how DHA suppresses seizures, focusing on the regulation of 17β-estradiol synthesis in the brain. Dietary supplementation with DHA increased not only the expression of P450arom, but also 17β-estradiol in the cerebral cortex. While DHA did not affect the duration or scores of the seizures induced by pentylenetetrazole, DHA significantly prolonged the seizure latency. A P450arom inhibitor, letrozole, reduced 17β-estradiol levels and completely suppressed the elongation of seizure latency elicited by DHA. These results suggest that DHA delays the onset of seizures by promoting the synthesis of 17β-estradiol in the brain. DHA upregulated the expression of anti-oxidative enzymes in the cerebral cortex. The oxidation in the cerebral cortex induced by pentylenetetrazole was significantly attenuated by DHA, and letrozole completely inhibited this suppressive action. Thus, the anti-oxidative effects of 17β-estradiol may be involved in the prevention of seizures mediated by DHA. This study revealed that 17β-estradiol in the brain mediated the physiological actions of DHA.
登录
查看更多内容
影响因子：
--
作者：
Ishihara Y;Takemoto T;Ishida A;Yamazaki T
通讯作者：
Yamazaki T
DOI：
10.1016/j.jsbmb.2014.10.002
发表时间：
2015-01-01
影响因子：
4.1
作者：
Ishihara, Yasuhiro;Itoh, Kouichi;Yamazaki, Takeshi
通讯作者：
Yamazaki, Takeshi
影响因子：
5.3
作者：
Hoffman, GE;Moore, N;Murphy, AZ
通讯作者：
Murphy, AZ
DOI：
10.1016/j.jsbmb.2005.02.016
发表时间：
2005-06-01
影响因子：
4.1
作者：
Carswell, HVO;Dominiczak, AF;Macrae, IM
通讯作者：
Macrae, IM
影响因子：
56.9
作者：
de Urquiza, AM;Liu, SY;Perlmann, T
通讯作者：
Perlmann, T