Serotonin 2C receptor contributes to gender differences in stress-induced hypophagia in aged mice.
Serotonin 2C receptor contributes to gender differences in stress-induced hypophagia in aged mice.
复制标题
血清素 2C 受体导致老年小鼠应激性吞咽功能减退的性别差异。
DOI：
10.1016/j.psyneuen.2015.02.006
复制
发表时间：
2015
影响因子：
3.7
通讯作者：
Takeda H
中科院分区：
文献类型：
--
作者：
Yamada C;Sadakane C;Nahata C;Saegusa Y;Nakagawa K;Okubo N;Ohnishi S;Hattori T;Takeda H
抑郁症和厌食症的结合可能会影响老年人的发病率和进行性身体残疾。应激后下丘脑-垂体-肾上腺轴的激活存在性别差异。本研究旨在探讨老年小鼠在新奇应激下摄食行为的性别差异。通过摄食量测定、免疫组化和mRNA表达分析，探讨5-羟色胺2C受体（5-HT 2CR）在应激性老年小鼠摄食抑制中的作用及其与ghrelin的关系。老年雄性小鼠暴露于新奇应激后，血浆皮质酮升高21倍，摄食量明显受到抑制。此外，5-HT 2CR激动剂抑制老年雄性小鼠的食物摄入。新奇应激诱导老年雄性小鼠下丘脑室旁核5-HT 2CR和c-Fos共表达细胞增加7倍，但对老年雌性小鼠无影响。血浆酰化ghrelin水平下降，强调老年雄性小鼠和管理的5-HT 2CR拮抗剂抑制这种下降。5-HT 2CR拮抗剂还逆转了雌激素受体α激动剂处理的老年雄性小鼠的摄食抑制。因此，在新奇应激暴露的老年雄性小鼠中显著抑制的进食行为可能是由5-HT 2CR超敏反应介导的，导致低ghrelin血症。这种超敏反应可能部分是由于老年雄性小鼠雌激素受体激活所致。
The combination of depression and anorexia may influence morbidity and progressive physical disability in the elderly. Gender differences exist in hypothalamic–pituitary–adrenal axis activation following stress exposure. The objective of this study was to investigate gender differences in feeding behavior under novelty stress in aged mice. Food intake measurement, immunohistochemical assessment, and mRNA expression analysis were conducted to investigate the role of serotonin 2C receptor (5-HT2CR) and its relationship with ghrelin in stress-induced suppression of feeding behavior in aged mice. After exposure to novelty stress, a 21-fold increase in plasma corticosterone and remarkable suppression of food intake were observed in aged male mice. Furthermore, a 5-HT2CR agonist suppressed food intake in aged male mice. Novelty stress induced a 7-fold increase in 5-HT2CR and c-Fos co-expressing cells in the paraventricular nucleus of the hypothalamus in aged male mice but caused no change in aged female mice. Plasma acylated ghrelin levels decreased in stressed aged male mice and administration of the 5-HT2CR antagonist inhibited this decrease. The 5-HT2CR antagonist also reversed the suppression of food intake in estrogen receptor α agonist-treated aged male mice. Therefore, conspicuously suppressed feeding behavior in novelty stress-exposed aged male mice may be mediated by 5-HT2CR hypersensitivity, leading to hypoghrelinemia. The hypersensitivity may partly be due to estrogen receptor activation in aged male mice.