Psychological stress in aged female mice causes acute hypophagia independent of central serotonin 2C receptor activation.
Psychological stress in aged female mice causes acute hypophagia independent of central serotonin 2C receptor activation.
复制标题
DOI：
10.1371/journal.pone.0187937
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Takeda H
中科院分区：
文献类型：
--
作者：
Matsumoto C;Yamada C;Sadakane C;Nahata M;Hattori T;Takeda H
应激后下丘脑-垂体-肾上腺轴的激活存在性别差异，并且应激反应进一步受到衰老的影响。本研究旨在阐明应激导致老年雌性小鼠食欲减退的机制。应激负荷后，老年雌性小鼠立即表现出急性食欲减退和血浆皮质酮水平上升。5-羟色胺2C受体（5-HT 2CR）拮抗剂的管理抑制血浆皮质酮，但不影响减少食物摄入量。相反，内源性生长激素释放肽增强剂，rikkunshito（RKT），显着抑制食物摄入量的减少。在禁食期间外周酰化生长素水平增加，这发生在年轻小鼠中，在老年雌性小鼠中没有观察到。此外，在这些小鼠中，在进食状态下观察到生长素释放肽和胃前生长素原mRNA表达水平显著增加。此外，血浆ghrelin水平升高RKT，而不是由5-HT 2CR拮抗剂。在雌性小鼠中，下丘脑非编辑（INI）和部分编辑的mRNA 5-HT 2CR亚型（VNV，VNI，VSV或VSI）随着年龄的增长而减少，而在雄性小鼠中，编辑亚型不受衰老或应激的影响。应激组和对照组雄性小鼠弓状核雌激素受体α（ERα）阳性细胞数均较对照组增加。应激组老年雄性小鼠室旁核ERα阳性细胞数较对照组明显增多，而雌性小鼠室旁核ERα阳性细胞数无明显增加。老年雌性小鼠暴露于压力下的食欲减退可能独立于5-HT 2CR激活。其机制可能与5-HT 2CR mRNA表达、外周酰基化ghrelin分泌和/或下丘脑ERα表达的性别依赖性差异调节有关。
Sex differences exist in the activation of the hypothalamic–pituitary–adrenal axis following exposure to stress, and the stress response is further affected by aging. This study was conducted to elucidate the mechanism of hypophagia in aged female mice exposed to stress. Immediately after a stress load, aged female mice exhibited acute hypophagia and a rise in plasma corticosterone levels. The administration of a serotonin 2C receptor (5-HT2CR) antagonist suppressed plasma corticosterone but did not affect the reduction in food intake. In contrast, an endogenous ghrelin enhancer, rikkunshito (RKT), significantly inhibited the reduction in food intake. An increase in peripheral acylated ghrelin levels during fasting, which occurs in young mice, was not observed in aged female mice. Moreover, in these mice, significantly increased levels of ghrelin and gastric preproghrelin mRNA expression were observed in the fed status. Moreover, plasma ghrelin levels were elevated by RKT and not by the 5-HT2CR antagonist. In female mice, the hypothalamic non-edited (INI) and partially edited mRNA 5-HT2CR isoforms (VNV, VNI, VSV or VSI) decreased with age, while in male mice, the editing isoform was unchanged by aging or stress. Estrogen receptor α (ERα)-positive cell counts in the arcuate nucleus of young male mice exposed to stress and control aged male mice were increased compared with those in young control mice. In aged male mice exposed to stress, the number of ERα-expressing cells in the paraventricular nucleus were significantly increased compared with those in aged control mice; in female mice, there was no increase in the number of ERα-positive cells. Hypophagia in aged female mice exposed to stress may be independent of 5-HT2CR activation. It seems likely that the mechanisms may be caused by sex dependent, differential regulation in 5-HT2CR mRNA expression, peripheral acylated ghrelin secretion and/or hypothalamic ERα expression.
登录
查看更多内容
影响因子：
3.4
作者：
Cruz, APM;Pinheiro, G;Landeira-Fernandez, J
通讯作者：
Landeira-Fernandez, J
影响因子：
3
作者：
Lanfranco, Maria Fe;Seitz, Patricia K.;Cunningham, Kathryn A.
通讯作者：
Cunningham, Kathryn A.
影响因子：
6.8
作者：
Fujitsuka N;Asakawa A;Uezono Y;Minami K;Yamaguchi T;Niijima A;Yada T;Maejima Y;Sedbazar U;Sakai T;Hattori T;Kase Y;Inui A
通讯作者：
Inui A
影响因子：
11
作者：
Fujitsuka, N.;Asakawa, A.;Morinaga, A.;Amitani, M. S.;Amitani, H.;Katsuura, G.;Sawada, Y.;Sudo, Y.;Uezono, Y.;Mochiki, E.;Sakata, I.;Sakai, T.;Hanazaki, K.;Yada, T.;Yakabi, K.;Sakuma, E.;Ueki, T.;Niijima, A.;Nakagawa, K.;Okubo, N.;Takeda, H.;Asaka, M.;Inui, A.
通讯作者：
Inui, A.
影响因子：
7.4
作者：
Handa RJ;Weiser MJ
通讯作者：
Weiser MJ