Right vagus nerve stimulation improves motor behavior by exerting neuroprotective effects in Parkinson’s disease rats

BACKGROUND: Parkinson’s disease (PD) is a common movement disorder disease. Left vagus nerve stimulation (LVNS) is a potential treatment option for PD. Compared with the left vagus nerve, the right vagus nerve is more closely connected with the midbrain dopaminergic neurons, which are the lesion locations of PD. However, whether right vagus nerve stimulation (RVNS) has a therapeutic effect on PD has not yet been studied. Therefore, in this study, we studied the therapeutic effect and underlying mechanism of RVNS using a PD rat model. METHODS: To establish the PD rat model, 8-week-old male Sprague-Dawley rats were intraperitoneally injected with rotenone for 21 days. The cuff electrodes were implanted into the right cervical vagal carotid sheaths of the rats. The right vagus nerve was continuously stimulated for 14 days using a radio stimulation system. Behavioral tests were performed before and after stimulation. Finally, tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and α-synuclein in the midbrain, including the substantia nigra (SN) and ventral tegmental area (VTA), were detected by immunofluorescence. RESULTS: A markedly lower distance traveled and rearing number was observed in the rotenone, rotenone + sham, and rotenone + RVNS groups compared to the vehicle group. After the stimulation days, the distance traveled and rearing number were both higher in the rotenone + RVNS group compared to the rotenone and rotenone + sham groups (P<0.01, P<0.0001). A remarkable increase in distance traveled and rearing number was observed in the rotenone + RVNS group after stimulation. TH expression in the vehicle group was significantly up-regulated than the other groups. RVNS markedly up-regulated TH expression level. A significantly higher expression of α-synuclein was observed in the rotenone, rotenone + sham, and rotenone + RVNS groups compared to the vehicle group. The expression of α-synuclein was lower in the rotenone + RVNS group compared to the rotenone and rotenone + sham groups. A markedly higher VMAT2 expression was observed in the vehicle group compared to other groups. RVNS significantly up-regulated VMAT2 expression. CONCLUSIONS: The improved motor behavior and neuroprotective effects on the midbrain dopaminergic neurons in the PD rat model suggest that RVNS could be used as a potential treatment for PD.