ツジ マユミ   Tsuji Mayumi
  辻 真弓
   所属   医学部医学科  基礎医学系 衛生学
   職種   教授
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid.
掲載誌名 正式名:Scientific reports
略  称:Sci Rep
ISSNコード:20452322/20452322
巻・号・頁 7(1),6268頁
著者・共著者 Ishihara Yasuhiro, Itoh Kouichi, Tanaka Miki, Tsuji Mayumi, Kawamoto Toshihiro, Kawato Suguru, Vogel Christoph F A, Yamazaki Takeshi
発行年月 2017/07
概要 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.
DOI 10.1038/s41598-017-06630-0
PMID 28740157