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Vulnerability to psychological stress-induced anorexia in female mice depends on blockade of ghrelin signal in nucleus tractus solitarius

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Title: Vulnerability to psychological stress-induced anorexia in female mice depends on blockade of ghrelin signal in nucleus tractus solitarius
Authors: Yamada, Chihiro Browse this author
Iizuka, Seiichi Browse this author
Nahata, Miwa Browse this author
Hattori, Tomohisa Browse this author
Takeda, Hiroshi Browse this author →KAKEN DB
Keywords: anorexia
ghrelin
mice
rikkunshito
sex differences
stress
Issue Date: Oct-2020
Publisher: John Wiley & Sons
Journal Title: British journal of pharmacology
Volume: 177
Issue: 20
Start Page: 4666
End Page: 4682
Publisher DOI: 10.1111/bph.15219
PMID: 32754963
Abstract: Background and Purpose Women have a higher incidence of eating disorders than men. We investigated whether the effects of ghrelin on feeding are affected by sex and stress, and to elucidate the mechanisms that may cause sex differences in stress-mediated anorexia, focusing on ghrelin. Experimental Approach Acylated ghrelin was administered to naive and psychologically stressed male and female C57BL/6J mice, followed by measurements of food intake and plasma hormone levels. Ovariectomy was performed to determine the effects of ovary-derived oestrogen on stress-induced eating disorders in female mice. The numbers ofAgrporc-FosmRNA-positive cells and estrogen receptor alpha/c-Fos protein-double-positive cells were assessed. Key Results Ghrelin administration to naive female mice caused a higher increase in food intake, growth hormone secretion,AgrpmRNA expression in the arcuate nucleus andc-Fosexpression in the nucleus tractus solitarius (NTS) than in male mice. In contrast, psychological stress caused a more sustained reduction in food intake in females than males. The high sensitivity of naive females to exogenous ghrelin was attenuated by stress exposure. The stress-induced decline in food intake was not abolished by ovariectomy. Estrogen receptor-alpha but not -beta antagonism prevented the decrease in food intake under stress. Estrogen receptor-alpha/c-Fos-double-positive cells in the NTS were significantly increased by stress only in females. Conclusion and Implications Stress-mediated eating disorders in females may be due to blockade of ghrelin signalling via estrogen receptor-alpha activation in the NTS. Targeting the ghrelin signal in the brain could be a new treatment strategy to prevent these disorders.
Rights: http://creativecommons.org/licenses/by-nc/4.0/
Type: article
URI: http://hdl.handle.net/2115/79574
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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