Therapeutic Effect And Mechanism Of Vagus Nerve Stimulation On Rat Model Of Parkinson’s Disease

Part I: Study on the therapeutic effect of vagus nerve stimulation on rat model of Parkinson’s diseaseObjective: To investigate the effect of vagus nerve stimulation on the behavior of rats with Parkinson’s disease(PD)and Left vagus nerve stimulation(LVNS)versus Right vagus nerve stimulation(RVNS).Methods: Fifty rats were randomly divided into solvent group,rotenone group,rotenone + sham operation group,rotenone +LVNS group and rotenone+RVNS group,with 10 rats in each group.The PD rat model was established by peritoneal injection of rotenone for 21 days.Cuff electrodes were implanted on the vagus carotid sheath in the neck of rats,and electrical vagus nerve stimulation was performed using an in vivo wireless stimulation system.Open field experiment,balance beam walking experiment and pole climbing experiment were conducted before and after stimulation.Results: Comparing rotenone +LVNS group and rotenone +RVNS group with rotenone group and rotenone + sham operation group after treatment,the proportions of total distance,standing times,average speed and central time in open field experiment were higher than those in rotenone group and rotenone + sham operation group(P<0.001),the total time and slip times of the balance beam walking experiment were lower than those of rotenone group and rotenone + sham group(P<0.001),the total time in the rod-climbing experiment was lower than that in rotenone group and rotenone + sham group(P<0.001).Compared with rotenone+LVNS group and rotenone +RVNS group before and after treatment,the proportions of total distance,standing times,average speed and central time in open field experiment were lower than those before treatment(P<0.001),the total time and slip times of balance beam walking experiment were higher before treatment than after treatment(P<0.001),the total time before treatment was higher than after treatment(P<0.001).Comparing rotenone +LVNS group with rotenone +RVNS group after treatment,the ratio of total distance,standing times,average speed and central time in open field experiment was lower in rotenone +LVNS group than in rotenone +RVNS group(P<0.01),the total time and slip times of rotenone +LVNS group were higher than those of rotenone +RVNS group(P<0.01),the total time of rotenone +LVNS group was higher than that of rotenone +RVNS group(P<0.01).Conclusion: Vagus nerve stimulation has therapeutic effect on PD rats,and can improve motor behavior disorder and non-motor behavior disorder in PD rats.RVNS has better therapeutic effect on PD rats than LVNS.Part II: studies the mechanism of vagus nerve stimulation on Parkinson’s disease ratsObjective: To study the effects of vagus nerve stimulation on the expression levels of DJ-1,Ca MK IV,VMAT2,Nurr1,CREB1,TH,α-Syn and dopamine levels in substantia nigra of PD rats,and to compare LVNS and RVNS.Methods: 44 rats were randomly divided into solvent group,rotenone group,rotenone +LVNS group and rotenone +RVNS group,with 11 rats in each group.The PD rat model was established by peritoneal injection of rotenone for 21 days.Cuff electrodes are implanted into the cervical vagus carotid sheath of rats for electrical vagus stimulation using an in vivo wireless stimulation system.After the stimulation,TH and α-Syn in the substantia nigra were detected by immunohistochemical detection and the immunofluorescence detection of DJ-1,Ca MK IV,VMAT2,Nurr1,TH and α-Syn were detected by immunohistochemical detection of the substantia nigra.The substantia nigra tissues of rats were collected for the determination of dopamine by LMS.Results: Rotenone +LVNS group and rotenone +RVNS group were compared with rotenone group,and immunohistochemical detection indicated increased TH expression(P<0.001)and α-Syn expression decreased(P<0.001),the expression of DJ-1,Ca MK IV,VMAT2,Nurr1 and TH increased by immunofluorescence detection(P<0.001)and α-Syn expression decreased(P<0.001),Western blot indicated increased CREB1 expression(P<0.001)and α-Syn expression decreased(P<0.001),LMS induced increased dopamine levels(P<0.001).Immunohistochemical test showed that TH expression increased in rotenone +RVNS group compared with rotenone +LVNS group(P<0.001)and α-Syn expression decreased(P<0.001),the expression of DJ-1,Ca MK IV,VMAT2,Nurr1 and TH increased by immunofluorescence detection(P<0.01)and α-Syn expression decreased(P<0.01),Western blot indicated increased CREB1 expression(P<0.01)and α-Syn expression decreased(P<0.01),LMS induced increased dopamine level(P<0.01).Conclusion: VNS can activate the DJ-1/Ca MK IV/CREB1 and DJ-1/Nurr1 pathways in dopaminergic neurons of substantia nigra in rats with Parkinson’s disease,improve the dopamine depletion state of substantia nigra and inhibit α-Syn,thus playing a neuroprotective role in dopaminergic neurons of substantia nigra.The neuroprotective effect of RVNS on dopaminergic neurons in substantia nigra was better than that of LVNS.