Atorvastatin ameliorates depressive behaviors via regulation of α7nAChR expression by PI3K/Akt-BDNF pathway in mice.

Autor: Yang C; Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, China., Ni HY; Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China., Yin JJ; School of Life Science, Nantong University, Nantong, Jiangsu, China., Zhou T; School of Life Science, Nantong University, Nantong, Jiangsu, China., Gu QX; School of Life Science, Nantong University, Nantong, Jiangsu, China. Electronic address: qiuxiang@ntu.edu.cn., Chen TT; Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, Jiangsu, China. Electronic address: cttrose@ntu.edu.cn., Cai CY; School of Life Science, Nantong University, Nantong, Jiangsu, China. Electronic address: caichengyun86@163.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2022 Feb 19; Vol. 593, pp. 57-64. Date of Electronic Publication: 2022 Jan 12.
DOI: 10.1016/j.bbrc.2022.01.034
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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