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論文
- タイトル
- タイトル（英）
- Hypocretin/orexin loss changes the hypothalamic immune response.
- 参照URL
- https://researchmap.jp/SleepLab/published_papers/28127953
- 著者
- 著者（英）
- Susumu Tanaka,Nae Takizawa,Yoshiko Honda,Taro Koike,Souichi Oe,Hiromi Toyoda,Tohru Kodama,Hisao Yamada
- 担当区分
- 概要
- 概要（英）
- Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy.
- 出版者・発行元
- 出版者・発行元（英）
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- 誌名
- 誌名（英）
- Brain, behavior, and immunity
- 巻
- 57
- 号
- 開始ページ
- 58
- 終了ページ
- 67
- 出版年月
- 2016年10月
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- 0889-1591
- DOI URL
- https://doi.org/10.1016/j.bbi.2016.06.009
- 共同研究・競争的資金等の研究課題
研究者
児玉 亨
( )