我系的研究论文《Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates depressive-like behavior in a mouse model of chronic stress》于2017年12月在神经科学和神经炎症领域杂志《J Neuroinflammation》发表。我系硕士研究生赵丹和教师徐旭林副教授为第一作者，吕青副教授为通讯作者。
该研究采用慢性束缚应激（CRS）模型，探讨了α7烟碱型乙酰胆碱受体在CRS诱导的动物学习记忆损伤和抑郁样行为，及脑组织炎症反应的调节作用， 研究发现α7烟碱型乙酰胆碱受体激动剂DMXBA改善CRS小鼠学习记忆损伤和神经元损伤，进一步研究发现该作用与DMXBA调节TLR4/NF-KB促炎信号通路和Ach抗炎信号通路从而改善慢性应激过程中脑组织炎症反应有关。该研究为α7烟碱型乙酰胆碱受体及其激动剂保护慢性应激所致的海马损伤提供了实验数据和理论线索。
附：
J Neuroinflammation.2017 Dec 2;14(1):234. doi: 10.1186/s12974-017-1007-2.
Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates depressive-like behavior in a mouse model of chronic stress.
Zhao D,Xu X,Pan L,Zhu W,Fu X,Guo L,Lu Q,Wang J
Abstract
BACKGROUND:
It has been shown that chronic stress-induced depression is associated with exaggerated inflammatory response in the brain. Alpha7 nicotinic acetylcholine receptors (α7nAChRs) regulate the cholinergic anti-inflammatory pathway, but the role of cholinergic signaling and α7nAChR in chronic stress has not yet been examined.
METHODS:
In this study, we used a well-documented model of depression in which mice were exposed to 6 h of restraint stress for 21 consecutive days. Components of cholinergic signaling and TLR4 signaling were analyzed in the hippocampus. The main targets of neuroinflammation and neuronal damage were also evaluated after a series of tests for depression-like behavior.
RESULTS:
Chronic restraint stress (CRS) induced alterations in components of central cholinergic signaling in hippocampus, including increases in choline acetyltransferase protein expression and decreases in nuclear STAT3 signaling. CRS also increased TLR4 signaling activity, interleukin-1β, and tumor necrosis factor-α expression, microglial activation, and neuronal morphologic changes. Cholinergic stimulation with the α7nAChR agonist DMXBA significantly alleviated CRS-induced depressive-like behavior, neuroinflammation, and neuronal damage, but these effects were abolished by the selective α7nAChR antagonist α-bungarotoxin. Furthermore, activation of α7nAChRs restored the central cholinergic signaling function, inhibited TLR4-mediated inflammatory signaling and microglial activity, and increased the number of regulatory T cells in the hippocampus.
CONCLUSIONS:
These findings provide evidence that α7nAChR activation mitigates CRS-induced neuroinflammation and cell death, suggesting that α7nAChRs could be a new therapeutic target for the prevention and treatment of depression.
