Department of Oriental Medicine, Daejeon University, Daejeon, Korea.
Department of Microbiology and Biotechnology, Daejeon University, Daejeon, Korea.
Eur J Neurosci. 2019 Jul;50(1):1820-1830. doi: 10.1111/ejn.14368. Epub 2019 Mar 6.
A growing body of evidence shows that the electrical stimulation of the vagus nerve can improve mental illness including depression. Here, we investigated whether the vagus nerve stimulation (VNS) is involved in regulating the responsiveness of hippocampal neurons in rats under chronic restraint stress (CRS). c-Fos protein signals were detected 2 hr after VNS in 5-HT receptor-positive neurons in the dorsal raphe nucleus (DRN) as well as in the nucleus tractus solitarius (NTS). Chronic VNS was performed on a daily basis for 2 weeks using an implanted microelectrode in rats that had undergone CRS for 2 weeks. We found that the levels of both 5-HT receptors and phospho-Erk1/2 were decreased in parallel in the hippocampal neurons of CRS animals and then increased to the baseline levels by chronic VNS. Hippocampal induction of 5-HT receptors and phospho-Erk1/2 by VNS was diminished after the injection of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin of serotonergic neurons, into the DRN. Hippocampal production of brain-derived neurotrophic factor (BDNF) was also upregulated by VNS, but the treatment of 5,7-DHT abrogated the effects of VNS on BDNF induction. VNS in CRS animals improved the behavioral scores in forced swimming test (FST) compared to sham-stimulated control. Our results suggest that VNS-mediated serotonergic input via 5-HT receptors into the hippocampal neurons may activate BDNF pathway and improve depressive-like behaviors in CRS animals.
越来越多的证据表明，刺激迷走神经可以改善包括抑郁症在内的精神疾病。在这里，我们研究了迷走神经刺激（VNS）是否参与调节慢性束缚应激（CRS）大鼠海马神经元的反应性。在 5-羟色胺受体阳性神经元的背侧中缝核（DRN）和孤束核（NTS）中，VNS 后 2 小时检测到 c-Fos 蛋白信号。在经历了 2 周 CRS 的大鼠中，使用植入的微电极每天进行 2 周的慢性 VNS。我们发现，CRS 动物海马神经元中的 5-HT 受体和磷酸化-Erk1/2 水平平行下降，然后通过慢性 VNS 增加到基线水平。DRN 中 5,7-二羟基色胺（5,7-DHT），一种 5-羟色胺能神经元的神经毒素，注射后，VNS 诱导的海马 5-HT 受体和磷酸化-Erk1/2 减少。VNS 还上调了脑源性神经营养因子（BDNF）的产生，但 5,7-DHT 的处理消除了 VNS 对 BDNF 诱导的影响。与假刺激对照相比，CRS 动物中的 VNS 改善了强迫游泳试验（FST）中的行为评分。我们的结果表明，VNS 通过 5-HT 受体介导的迷走神经传入到海马神经元可能激活 BDNF 通路，并改善 CRS 动物的抑郁样行为。
