Possible Role Of The Habenula Nucleus In Levodopa-induced Dyskinesia With Parkinson's Rats

Dyskinesia is an abnormal involuntary movement produced by the treatment of Parkinson's disease with levodopa,which seriously affects the patient's health and life.Studies have shown that the lateral habenula plays an important role in the pathogenesis of Parkinson's disease.The lateral habenula has been proved to be connected with the nigrostriatal system while it was the important project target of the dopamine neurons from the substantia nigra pars compacta.What's more is that dopaminergic neurons spread over the lateral habenula.Therefore,it is speculated that the lateral habenula may play an important role in mediating the treatment of Parkinson-induced dyskinesia.This research will explore the possible mechanism of the lateral habenula nucleus in the treatment of Parkinson-induced dyskinesia.we injected 6-hydroxydopamine into the medial forebrain of Wistar rats to prepared the Parkinson rat models.The Parkinson rat models were then treated with levodopa(ip,daily)to get levodopa-induced dyskinesia module rats and the abnormal involuntary movements were scored once a week.Next,we tested the expression of related protein in the lateral habenula by Western blot.Finally,the mean frequency of the lateral habenula neurons of the injection side and the opposite side was measured by multi-channel electrophysiological recording technique.Results indicated that: the abnormal involuntary movements scores became higher with the prolonged administration of time;dopamine D1 receptor expression in the habenula of dyskinesia rats was higher on the 6-hydroxydopamine injection side than on the opposite side;as for the 6-hydroxydopamine injection side of the expression of dopamine D1 receptors and Beclin1 in the lateral habenula,dyskinesia rats were higher than that of Parkinson rats;the electrophysiology data demonstrated that the mean firing frequency of lateral habenula neurons in the 6-hydroxydopamine injection side of dyskinesia rats is higher than that of the opposite side.These results reveal that the increase of the firing frequency may be related to the dyskinesia and the increased expression of D1 R receptor may be one of the reasons for the increased activity of LHb neurons;Autophagy may be involved in the produce of LID which need further exploration.This study provides a basis for further exploring the role of the lateral nucleus in the development of dyskinesia.