Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid
Abstract 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 aromatas...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2017-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06630-0 |
| _version_ | 1818431511661117440 |
|---|---|
| author | Yasuhiro Ishihara Kouichi Itoh Miki Tanaka Mayumi Tsuji Toshihiro Kawamoto Suguru Kawato Christoph F. A. Vogel Takeshi Yamazaki |
| author_facet | Yasuhiro Ishihara Kouichi Itoh Miki Tanaka Mayumi Tsuji Toshihiro Kawamoto Suguru Kawato Christoph F. A. Vogel Takeshi Yamazaki |
| author_sort | Yasuhiro Ishihara |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-14T15:50:28Z |
| format | Article |
| id | doaj.art-f622cc0973304afc8cc9c6885c665567 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:50:28Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f622cc0973304afc8cc9c6885c6655672022-12-21T22:55:23ZengNature PortfolioScientific Reports2045-23222017-07-017111110.1038/s41598-017-06630-0Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acidYasuhiro Ishihara0Kouichi Itoh1Miki Tanaka2Mayumi Tsuji3Toshihiro Kawamoto4Suguru Kawato5Christoph F. A. Vogel6Takeshi Yamazaki7Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima UniversityLaboratory for Brain Science, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri UniversityLaboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima UniversityDepartment of Environmental Health, University of Occupational and Environmental HealthDepartment of Environmental Health, University of Occupational and Environmental HealthDepartment of Biophysics and Life Sciences, Graduate School of Arts and Sciences, University of TokyoCenter for Health and the Environment, University of California, DavisLaboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima UniversityAbstract 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.https://doi.org/10.1038/s41598-017-06630-0 |
| spellingShingle | Yasuhiro Ishihara Kouichi Itoh Miki Tanaka Mayumi Tsuji Toshihiro Kawamoto Suguru Kawato Christoph F. A. Vogel Takeshi Yamazaki Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid Scientific Reports |
| title | Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid |
| title_full | Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid |
| title_fullStr | Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid |
| title_full_unstemmed | Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid |
| title_short | Potentiation of 17β-estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid |
| title_sort | potentiation of 17β estradiol synthesis in the brain and elongation of seizure latency through dietary supplementation with docosahexaenoic acid |
| url | https://doi.org/10.1038/s41598-017-06630-0 |
| work_keys_str_mv | AT yasuhiroishihara potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid AT kouichiitoh potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid AT mikitanaka potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid AT mayumitsuji potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid AT toshihirokawamoto potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid AT sugurukawato potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid AT christophfavogel potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid AT takeshiyamazaki potentiationof17bestradiolsynthesisinthebrainandelongationofseizurelatencythroughdietarysupplementationwithdocosahexaenoicacid |