抗抑郁药
脑源性神经营养因子
原肌球蛋白受体激酶B
PI3K/AKT/mTOR通路
烟碱乙酰胆碱受体
神经营养因子
药理学
蛋白激酶B
海马体
化学
烟碱激动剂
突触可塑性
内分泌学
突触蛋白I
内科学
神经科学
医学
磷酸化
生物
信号转导
受体
生物化学
小泡
膜
突触小泡
作者
Chao Yang,Huanyu Ni,Jia-Jie Yin,Ting Zhou,Qiuxiang Gu,Tingting Chen,Cheng-Yun Cai
标识
DOI:10.1016/j.bbrc.2022.01.034
摘要
Some of the statins have been shown to have antidepressant effects, but whether atorvastatin (AV) has antidepressant effects is unknown. This study was to investigate the effect of AV treatment on depressive behaviors. Herein, we show that AV treatment had antidepressant-like effect in physiological conditions and antidepressant effect in depressive state which depended on α7 nicotinic acetylcholine receptor (α7nAChR) expression in the ventral hippocampus (vHPC), but not α4β2 nicotinic acetylcholine receptor (α4β2nAchR) expression in vHPC, nor the α7nAChR and α4β2nAchR expression in dorsal hippocampus (dHPC). By using MLA, a selective α7nAChR antagonist, we investigated the role of α7nAChR in AV treatment. Behavior tests demonstrated that MLA abolished the antidepressant effect of AV. Besides, our data showed that AV treatment increased Akt phosphorylation, brain-derived neurotrophic factor (BDNF), synaptic related protein synapsin and spinophilin expression. The phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 reversed AV-induced increase of BDNF expression, newborn neurons and antidepressant behavior effects. Our study suggests that AV plays an antidepressant role by regulating synaptic plasticity of vHPC through PI3K/Akt-BDNF signaling pathway, which may be a good choice for depression treatment.
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