Antidepressive‐like effect of a Kampo (traditional Japanese) medicine, kososan (Xiang Su San) in a stress‐induced depression‐like mouse model: Proteomic analysis of hypothalamus. Issue 2 (9th April 2015)

• Record Type: Journal Article
• Authors: Nagai, Takayuki; Hashimoto, Ryoko; Okuda, Sari M.; Kodera, Yoshio; Oh‐Ishi, Masamichi; Maeda, Tadakazu; Ito, Naoki; Hanawa, Toshihiko; Kiyohara, Hiroaki; Yamada, Haruki
• Is Part Of: Traditional & Kampo Medicine. Volume 2:Issue 2(2015)
• Page Start: 50
• Page End: 59
• Publication Date: 2015-04-09
• Subjects: 2′, 3′‐cyclic nucleotide 3′‐phosphodiesterase -- antidepressant -- kososan -- metabotropic glutamate receptor 2 -- proteomic analysis -- Xiang Su San; Medicine, Oriental -- Japan -- Periodicals; Medicine, Chinese -- Japan -- Periodicals; Medicine, East Asian Traditional; Japan; Medicine, Chinese; Medicine, Oriental; Japan; Electronic journals; Periodicals; Periodicals; 615
• DOI: 10.1002/tkm2.1018
• Languages: English
• ISSNs: 2053-4515

Abstract

ABSTRACT: Aim: A Kampo medicine, kososan (KS), has been used clinically for the treatment of certain depression‐like symptoms. Our previous studies using the stress‐induced depression‐like model mice, showed that oral KS treatment leads to an antidepressive‐like effect via the normalization of dysfunction of hypothalamic‐pituitary‐adrenal axis. In the present study, proteomic analysis was used to identify brain hypothalamus proteins that are affected by KS treatment. Methods: KS was orally administered to stress‐induced depression‐like model mice at 1.0 g/kg/day for 9 days, and the hypothalamus was then analyzed using agarose 2‐D gel electrophoresis, followed by mass spectrometry‐based protein identification, and then western blot analysis and immunohistochemical analysis. Results: The expression of eight proteins was increased or decreased in the hypothalamus of the model mice, but recovered on oral KS treatment. Among them, metabotropic glutamate receptor 2 (mGluR2) and 2′, 3′‐cyclic nucleotide 3′‐phosphodiesterase 1 (CNPase1) were identified as depression‐related proteins. Western blot of the hypothalamus confirmed these results and showed that the expression of CNPase2 was opposite to that of CNPase1. On immunohistochemistry, mGluR2 expression in the hypothalamus paraventricular nucleus was downregulated and CNPase2 expression was upregulated in the cerebral fornix in the model mouse, but KS returned them to normal. Conclusion: mGluR2 and CNPase in the hypothalamus are associated with the antidepressive‐like activity of KS.