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
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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