Danshensu Interventions Mediate Rapid Antidepressant Effects by Activating the Mammalian Target of Rapamycin Signaling and Brain-Derived Neurotrophic Factor Release

• 발행기관: 대한신경정신의학회
• 저자명: Han-Wen Chuang Chih-Chia Huang Kuang-Ti Chen Yen-Yu Kuo Jou-Hua Ren Tse-Yen Wang Mang-Hung Tsai Po-Ting Chen I-Hua Wei
• 간행물 정보: 『Psychiatry Investigation』제21권 제11호, 1286~1298쪽, 전체 13쪽
• 주제분류: 의약학 > 정신과학
• 파일형태: PDF
• 발행일자: 2024.11.18

국문 초록

Objective Danshensu, a phenylpropanoid compound, is derived from the dry root and rhizome of Danshen (Salvia miltiorrhiza), a traditional Chinese medicinal herb. Evidence suggests that danshensu protects isolated rat hearts against ischemia/reperfusion injury by activating the protein kinase B (Akt)/extracellular signal-regulated kinase (ERK) pathway or by inhibiting autophagy and apoptosis through the activation of mammalian target of rapamycin (mTOR) signaling. Furthermore, danshensu promotes the postischemic regeneration of brain cells by upregulating the expression of brain-derived neurotrophic factor (BDNF) in the peri-infarct region. However, basic and clinical studies are needed to investigate the antidepressant effects danshensu and determine whether brain mTOR signaling and BDNF activation mediate these effects. The aforementioned need prompted us to conduct the present study. Methods Using a C57BL/6 mouse model, we investigated the antidepressant-like effects of danshensu and the mechanisms that mediate these effects. To elucidate the mechanisms, we analyzed the roles of Akt/ERK–mTOR signaling and BDNF activation in mediating the antidepressant-like effects of danshensu. Results Danshensu exerted its antidepressant-like effects by activating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) of Akt/ERK–mTOR signaling and promoting BDNF release. Treatment with danshensu increased the level of glutamate receptor 1 phosphorylation at the protein kinase A site. Conclusion Our study may be the first to demonstrate that the antidepressant effects of danshensu are dependent on the activation of the AMPAR–mTOR signaling pathway, are correlated with the elevation of BDNF level, and facilitate the insertion of AMPAR into the postsynaptic membrane. This study also pioneers in unveiling the potential of danshensu against depressive disorders.

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키워드

Danshensu α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor Mammalian target of rapamycin Brain-derived neurotrophic factor Antidepressant