PNU282987 alleviates Aβ-induced anxiety and depressive-like behaviors through upregulation of α7nAChR by ERK-serotonin receptors pathway

开阔地 高架加迷宫 MAPK/ERK通路 行为绝望测验 兴奋剂 受体 5-羟色胺受体 p38丝裂原活化蛋白激酶 内分泌学 化学 内科学 扁桃形结构 抗抑郁药 心理学 下调和上调 信号转导 海马体 血清素 焦虑 医学 精神科 生物化学 基因
作者
Ke-Wei Chang,Hang-Fan Zong,Meng Wang,Mohammad Yasir Rizvi,Saema Iffat Neha,Weina Yang,Shengfeng Ji,Yanbing Ma,Yi‐Hua Qian
出处
期刊:Neuroscience Letters [Elsevier]
卷期号:731: 135118-135118 被引量:6
标识
DOI:10.1016/j.neulet.2020.135118
摘要

Patients with Alzheimer's disease often undergo anxiety and depression. Our previous studies have shown that α7nAChR protects against Aβ-induced neurotoxicity via downregulation of p38 and JNK MAPKs, but the role of α7nAChR on Aβ-induced anxiety and depressive-like behaviors and the effect of α7nAChR on the regulation of MAPKs pathways remain unknown. To examine the effects of α7nAChR and MAPKs pathways on Aβ-induced anxiety and depression-like behaviors and to explore their relationships between them, elevated plus maze, open field and forced swim tests were performed. Protein levels of 5-HT1A receptor, 5-HT2C receptor, α7nAChR, t-ERK1/2 and p-ERK1/2 in the amygdala were analyzed by western blotting and immunostaining. Our study found out that Aβ oligomers induced anxiety and depression-like behaviors in C56BL/6 mice with open field, elevated plus maze and forced swim tests. However, activation of α7nAChR or inhibition of ERK pathways showed significant antidepressant and anxiolytic-like effects on Aβ-injected mice. Moreover, Aβ significantly decreased the level of 5-HT1A receptor but increased the level of 5-HT2C receptor in the basolateral amygdala. Treatment with α7nAChR agonist PNU282987 or ERK inhibitor U0126 reversed Aβ-induced 5-HT1A and 5-HT2C receptor changes. Moreover, activation of α7nAChR inhibited ERK pathway in the amygdala of Aβ1−42-injected mice. Our study provides a new insight into the mechanism of α7nAChR in Aβ-induced depression and anxiety-related symptoms through the regulation of ERK1/2 pathway and the potential association with serotonin receptors. Together, our data suggests that α7nAChR is protective against Aβ-induced anxiety and depression-like behaviors in mice.
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