Amyloid β peptide 1–42 (Aβ_1-42) could induce cognitive deficits through oxidative stress, inflammation, and neuron death in Alzheimer's disease (AD). MAPK pathways have been thought to mediate Aβ_1-42-induced neuroinflammation responses, neuron death and cognitive decline in AD. The α7 nicotinic acetylcholine receptor (α7nAChR) exerts a neuroprotective effect. However, whether α7nAChR alleviates Aβ_1-42-induced neurotoxicity through MAPKs (p38, ERK, JNK) in vivo remains unclear. In our study, memory was assessed in C57BL/6 mice using a Y-maze test. Cell death was assessed by Nissl and Hoechst staining and Bax, Bcl-2, Caspase 3, and Cytochrome C levels using Western blotting. Oxidative stress was assayed by superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. Inflammation was examined with GFAP and Iba1 using immunohistochemistry. The Aβ degrading enzymes insulin degrading enzyme (IDE) and neprilysin (NEP) were tested using Western blotting. We found that activating α7nAChR or inhibiting p38 or JNK pathway alleviated Aβ_1-42-induced cognitive deficits and neuron loss and death by reducing oxidative stress. In addition, activating α7nAChR or inhibiting p38 or JNK pathway also reduced inflammation, which was observed as reduced GFAP and Iba1 levels with different effects on Aβ degrading enzymes. Finally, we found that the activation of α7nAChR led to the downregulation of pp38 and pJNK levels. Conversely, the inhibition of p38 or JNK resulted in the upregulation of α7nAChR levels in the hippocampus and cortex. Our data indicate that the activation of α7nAChR alleviates Aβ_1-42-induced neurotoxicity, and this protective effect might act through the downregulation of p38 and JNK MAPKs.

β淀粉样蛋白1-42（_Aβ1-42）可以通过阿尔茨海默病（AD）中的氧化应激，炎症和神经元死亡诱导认知缺陷。MAPK途径被认为可介导_Aβ1-42诱导的AD的神经炎症反应，神经元死亡和认知能力下降。α7烟碱乙酰胆碱受体（α7nAChR）发挥神经保护作用。然而，α7nAChR是否通过体内MAPKs（p38，ERK，JNK）减轻_Aβ1-42诱导的神经毒性还不清楚。在我们的研究中，使用Y迷宫测试评估了C57BL / 6小鼠的记忆力。使用Nissl和Hoechst染色以及Western印迹法评估Bax，Bcl-2，Caspase 3和细胞色素C的水平来评估细胞死亡。通过超氧化物歧化酶（SOD），过氧化氢酶（CAT）和丙二醛（MDA）含量测定氧化应激。使用免疫组织化学法用GFAP和Iba1检查炎症。使用蛋白质印迹法检测Aβ降解酶胰岛素降解酶（IDE）和中性溶酶（NEP）。我们发现激活α7nAChR或抑制p38或JNK途径可减轻_Aβ1-42减少氧化应激引起的认知障碍和神经元丧失及死亡。此外，激活α7nAChR或抑制p38或JNK途径也可以减少炎症，这是由于GFAP和Iba1含量降低，对Aβ降解酶的影响不同。最后，我们发现α7nAChR的激活导致pp38和pJNK水平的下调。相反，对p38或JNK的抑制导致海马和皮质中α7nAChR水平的上调。我们的数据表明，α7nAChR的激活减轻了_Aβ1-42诱导的神经毒性，这种保护作用可能通过下调p38和JNK MAPK发挥作用。