Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Dongcheng District, No.16 Dongzhimen Nan Xiao Street, Beijing, 100700, China.
J Neuroinflammation. 2021 Dec 17;18(1):291. doi: 10.1186/s12974-021-02341-6.
Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (-/-) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA).
There were control, model, taVNS, α7nAChR(-/-) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1β and the morphology of microglia were detected.
Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1β, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(-/-) rats and Hi MLA rats.
The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.
应激诱导的神经炎症被认为在抑郁症的发病机制中起关键作用。经皮耳迷走神经刺激（taVNS）是一种相对无创的替代治疗方法，适用于患有重度抑郁症的患者。迷走神经的抗炎信号是由α7 烟碱型乙酰胆碱受体（α7nAchR）介导的，而海马体是α7nAchR 分布最广的区域，它调节情绪。在这里，我们通过杂合子α7nAChR（-/-）基因敲除和α7nAchR 拮抗剂（甲基六氢槟榔碱，MLA）研究了海马体神经炎症中介的α7nAchR 在 taVNS 抗抑郁作用中的作用。
有对照组、模型组、taVNS 组、α7nAChR（-/-）+taVNS 组、海马体（Hi）MLA+taVNS 组和 Hi 盐水+taVNS 组。我们使用慢性不可预测轻度应激（CUMS）方法建立了 42 天的抑郁模型大鼠，除对照组外。建模成功后，除对照组和模型组外，其余各组大鼠均采用电针仪于耳廓（2/15 Hz，2 mA，30 min/d）进行 taVNS，共 21 天。行为测试在基线、建模后和 taVNS 干预后进行，包括蔗糖偏好测试（SPT）、旷场测试（OFT）和强迫游泳测试（FST）。这些测试广泛用于评估大鼠的抑郁样行为。实验结束后取样，检测α7nAchR、NF-κB p65、IL-1β的表达及小胶质细胞的形态。
CUMS 模型大鼠的抑郁样行为和海马体神经炎症表现为α7nAchR 表达下调，NF-κB p65 和 IL-1β 表达上调，小胶质细胞形态呈阿米巴样激活状态。taVNS 能显著逆转上述现象，但对α7nAChR（-/-）大鼠和 Hi MLA 大鼠的改善作用较小。
taVNS 的抗抑郁作用与海马体α7nAchR/NF-κB 信号通路有关。
