经皮耳迷走神经刺激通过调节中枢 α7nAChR/JAK2 信号传导减弱 LPS 诱导的抑郁样行为。
Transcutaneous Auricular Vagus Stimulation Attenuates LPS-Induced Depression-Like Behavior by Regulating Central α7nAChR/JAK2 Signaling.
发表日期:2024 Aug 30
作者:
Junying Wang, Yu Wang, Yu Chen, Jinling Zhang, Yue Zhang, Shaoyuan Li, Haohan Zhu, Xingke Song, Liwei Hou, Lei Wang, Yifei Wang, Zixuan Zhang, Peijing Rong
来源:
MOLECULAR NEUROBIOLOGY
摘要:
抑郁症是世界范围内一种严重的致残疾病。越来越多的证据支持抑郁症与炎症之间存在密切关系,那么抑制神经炎症可能是治疗抑郁症的另一种机制。经皮耳迷走神经刺激(taVNS)作为一种无创经皮电刺激,可以有效治疗抑郁症,但其机制尚不清楚。在这项研究中,通过腹腔注射脂多糖(LPS)诱导大鼠出现抑郁样行为。将大鼠随机分为对照组、LPS组、taVNS LPS组,与α7烟碱氯化乙酰胆碱受体(α7nAChR)(- / -)基因敲除大鼠相同。 Western blot检测下丘脑、杏仁核、海马肿瘤坏死因子α(TNF-ɑ)、磷酸化Janus激酶2(p-JAK2)、磷酸化信号转导子和转录激活子3(p-STAT3)的表达。我们观察到LPS显着降低了蔗糖偏好、进入高架十字迷宫开放臂的时间以及旷场试验中穿越和收获的次数。 TaVNS 治疗可改善这些抑郁样行为,但 taVNS 对 α7nAChR (- / -) 基因敲除大鼠无效。 LPS诱导的下丘脑和杏仁核中TNF-α表达显着升高,p-Jak2和p-STAT3表达显着降低。 TaVNS可显着逆转上述现象,但对α7nAChR(- / -)大鼠有罕见的改善作用。我们得出结论,taVNS 对 LPS 诱导的抑郁大鼠的抗抑郁作用与下丘脑和杏仁核中的 α7nAchR/JAK2 信号通路有关。© 2024。作者获得 Springer Science Business Media, LLC 的独家许可,该公司是施普林格自然。
Depression is a serious disabling disease worldwide. Accumulating evidence supports that there is a close relationship between depression and inflammation, and then inhibition of neuroinflammation may be another mechanism for the treatment of depression. Transcutaneous auricular vagus stimulation (taVNS), as a noninvasive transcutaneous electrical stimulation, could effectively treat depression, but its mechanism is unclear. In this study, rats with depression-like behavior were induced by intraperitoneal injection of lipopolysaccharide (LPS). The rats were randomly divided to control group, LPS group, taVNS + LPS group, and the same as the α7 nicotinic acetylcholine chloride receptor (α7nAChR) (- / -) gene knockout rats. The expressions of tumor necrosis factor alpha (TNF-ɑ) and phosphorylated-Janus kinase2 (p-JAK2), phosphorylated-signal transducer and activator of transcription3(p-STAT3) in the hypothalamus, amygdala, and hippocampus were detected by Western blot. We observed that LPS significantly decreased the sucrose preference, the time of into the open arms in the elevated plus maze, and the number of crossing and reaping in the open field test. TaVNS treatment improves these depression-like behaviors, but taVNS is not effective in α7nAChR (- / -) gene knockout rats. The expression of TNF-ɑ significantly increased, and the expression of p-Jak2 and p-STAT3 markedly decreased in the hypothalamus and amygdala induced by LPS. TaVNS could significantly reverse the abovementioned phenomena but had rare improvement effect for α7nAChR (- / -) rats. We conclude that the antidepressant effect of taVNS for LPS-induced depressive rats is related to α7nAchR/JAK2 signal pathway in the hypothalamus and amygdala.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.