Gomisin N ameliorates lipopolysaccharide-induced depressive-like behaviors by attenuating inflammation in the hypothalamic paraventricular nucleus and central nucleus of the amygdala in mice

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• 作者：Ryota Araki ; ^{r-araki@pharm.setsunan.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Yosuke Hiraki ; Shoji Nishida ; Yuka Inatomi ; Takeshi Yabe ; ^{yabe@pharm.setsunan.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Amygdala ; Depressive-like behavior ; Gomisin N ; Hypothalamus ; Lipopolysaccharide
• 刊名：Journal of Pharmacological Sciences
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：132
• 期：2
• 页码：138-144
• 全文大小：729 K

文摘

Emotional impairments such as depressive symptoms often develop in patients with sustained and systemic immune activation. The objective of this study is to investigate the effect of gomisin N, a dibenzocyclooctadiene lignan isolated from the dried fruits of Schisandra chinensis (Turcz.) Baill., which exhibited inhibitory effects of the bacterial endotoxin lipopolysaccharide (LPS)-induced NO production in a screening assay, on inflammation-induced depressive symptoms. We examined the effects of gomisin N on inflammation induced by LPS in murine microglial BV-2 cells and on LPS-induced behavioral changes in mice. Gomisin N inhibited LPS-induced expression of mRNAs for inflammation-related genes (inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α) in BV-2 cells. Administration of gomisin N attenuated LPS-induced expression of mRNAs for inflammation-related genes, increases in the number of c-Fos immunopositive cells in the hypothalamus and amygdala, depressive-like behavior in the forced swim test and exploratory behavior deficits 24 h after LPS administration in mice. These results suggest that gomisin N might ameliorate LPS-induced depressive-like behaviors through inhibition of inflammatory responses and neural activation in the hypothalamus and amygdala.