药丸
PI3K/AKT/mTOR通路
抗抑郁药
海马结构
医学
药理学
海马体
内分泌学
信号转导
神经科学
传统医学
化学
生物
生物化学
作者
Hailou Zhang,Yan Sun,Zihao Huang,Zhangjie Wu,Ying Yin,Ruiyi Liu,Jie Lin,Chuyuan Li,Gang Chen
标识
DOI:10.1016/j.jep.2023.117016
摘要
Jiawei-Xiaoyao pill (JWX), a traditional Chinese medicine, was recorded in ancient Chinese medicine pharmacopoeia using for treatment of various diseases, including mood disorders. Current mainstream antidepressants have a disadvantage in delayed onset of action. The rapid antidepressant potential of JWX and the underlying mechanisms remain unclear. We aimed to assess the rapid antidepressant potential of JWX, within the prescription dose range, and the distinct underlying neuroplasticity signaling mechanism. The rapid antidepressant response of JWX were determined using various behavioral paradigms, and in a corticosterone (CORT)-induced depression model in mice. The molecular neuroplasticity signaling and the expression of BDNF in the hippocampus was evaluated using immunoblotting and immunostaining. The contribution of specific signaling was investigated using pharmacological interventions. A single dose of JWX induced rapid and persistent antidepressant effects in both the normal and chronic CORT-exposed mice. The phosphorylation of CaMKII, mTOR, ERK and the expressions of BDNF, synapsin1 and PSD95 increased at 30 min post JWX. JWX restored the expression of BDNF in the hippocampal dentate gyrus reduced by CORT-exposure. The rapid antidepressant effect and upregulation of BDNF expression by JWX was blunted by a mTOR antagonist, rapamycin, or a CaMKII antagonist, KN-93. CaMKII signaling blockade blunted mTOR signaling activated by JWX, but not vice versa. JWX elicits a rapid antidepressant effect, via quickly stimulating CaMKII signaling, subsequently activating mTOR-BDNF signaling pathway, and thus enhancing hippocampal neuroplasticity.
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