Connexin36Was Over-expressed In The Rat Model Of The Levodopa-induced Dyskinesia

Objective: To explore the role of gap junction (GJ) in the pathonenesis oflevodopa-induced dyskinesia (LID) by observing the effects of GJ blockercarbenoxolone given systemicly on the apomorphine induced abnormal involuntarymovement (AIM) and the expression of connexin36(CX36) in the cerebral motorcortex and striatum region in rat model of LID.Methods: Hemi-parkinsonism(PD) models were made by stereotactic injection of6-hydroxydopamine(6-OHDA) to the right medial forebrain bundle (MFB) of adultmale SD rats. The PD rats received intraperitoneal injection of L-dopa(20mg/kg)+benserazide(5mg/kg) for21days consecutively in order to induce abnormal involuntarymovement, the AIM score was assessed according to a standard scoring criteria andthose with AIM scores more than20were defined as the successful LID models. Theexperimental animals were divided into three groups(each group has16rats): LIDgroup, PD group and normal control group. respectively, and each group was furtherlydivided into two subgroups (carbenoxolone group and saline group). Then, theapomorphine induced AIM and rotational behavior in responese to GJ blockercarbenoxolone given by intraperitoneal injection were assessed. After the behaviortesting, the rats were executed and processed for examining CX36expression in thestriatum and motor cortex by immunohistochemistry. Results: Complex involuntary movement behaviors could be observed for LID groupand contralateral rotation behavior were observed for PD group after given abdominalinjection of apomorphine (0.2mg/kg), but no significant behavior effects were detectedin response to pre-treatment of carbenoxolone by intraperitoneal injection on theseanimals, neither the AIM scores nor the rotational scores in the carbenoxolonepre-treatment subgroup showed significant difference from the saline pre-treatmentsubgroup(P>0.05). CX36expression were detected on striatum as well as motor cortex.The expression of CX36in striatum and motor cortex of LID rats was significantlyincreased compared with PD model or the normal control rats (P <0.05); Comparedwith the normal control group, CX36expression in these brain regions in the PD modelgroup was also elevated (P <0.05).Conclusion:(1) Intraperitoneal injection of GJ blocker carbenoxolone can’t improvethe involuntary movement in the LID rat model;(2) The expression of connexin36inthe striatum and cerebral motor cortex was increased in LID rats, GJ dysfunction mayplay a role in the pathogenesis of LID.(3) GJ may be involved in the dysfunction ofcortex-basal ganglia pathway of PD since there existed over-expression of CX36in thestriatum and motor cortex in the PD model.