Depressive symptoms as a side effect of Interferon-alpha therapy induced by induction of indoleamine 2,3-dioxygenase 1

• 村上, 由希

• 田代, 智之

• 西川, 元也

• 高橋, 有己

• 髙倉, 喜信

• 山本, 康子

• 斉藤, 邦明

• Takahashi, Yuki

• Takakura, Yoshinobu

• Mitani, Satoko

• Fujigaki, Hidetsugu

• Ohta, Yoshiji

• Kubo, Hisako

• Mamiya, Takayoshi

• Nabeshima, Toshitaka

• Kim, Hyoung-Chun

• Yamamoto, Yasuko

• Saito, Kuniaki

書誌事項

タイトル別名

• Depressive symptoms as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1

抄録

Depression is known to occur frequently in chronic hepatitis C viral (HCV) patients receiving interferon (IFN)-α therapy. In this study, we investigated whether indoleamine 2, 3-dioxygenase1 (IDO1)-mediated tryptophan (TRP) metabolism plays a critical role in depression occurring as a side effect of IFN-α therapy. Increases in serum kynurenine (KYN) and 3-hydroxykynurenine (3-HK) concentrations and in the ratios of KYN/TRP and 3-HK/kynurenic acid (KA) were much larger in depressive HCV patients than in non-depressed patients following therapy. Furthermore, transfection of a plasmid continuously expressing murine IFN-γ into normal mice significantly increased depression-like behavior. IFN-γ gene transfer also resulted in a decrease in serum TRP levels in the mice while KYN and 3-HK levels were significantly increased in both serum and frontal cortex. Genetic deletion of IDO1 in mice abrogated both the increase in depression-like behavior and the elevation in TRP metabolites’ levels, and the turnover of serotonin in the frontal cortex after IFN-γ gene transfer. These results indicate that the KYN pathway of IDO1-mediated TRP metabolism plays a critical role in depressive symptoms associated with IFN-α therapy.

収録刊行物

• Scientific Reports

  Scientific Reports 6 29920-, 2016-07-20

  Springer Nature

キーワード

• Depression
• Experimental models of disease

詳細情報

• CRID: 1050564285802714240
• NII論文ID: 120006323748
• ISSN: 20452322
• DOI: 10.1038/srep29920
• HANDLE: 2433/226364
• Web Site: https://www.nature.com/articles/srep29920.pdf
• Web Site: https://www.nature.com/articles/srep29920
• 本文言語コード: en
• 資料種別: journal article
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