Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid

Ishihara Yasuhiro

Itoh Kouichi

Tanaka Miki

Tsuji Mayumi

Kawamoto Toshihiro

Kawato Suguru

Vogel Christoph F. A.

Yamazaki Takeshi

Scientific Reports

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.

eng

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[ISSN] 2045-2322

[DOI] 10.1038/s41598-017-06630-0

[DOI] https://doi.org/10.1038/s41598-017-06630-0