Effects Of Aspirin On L-DOPA-induced Dyskinesia In Rat Parkinson's Disease Model

Objective: This study aimed to explore the effects of ASA on L-DOPA-induced-dyskinesia in rat model of Parkinson's disease and its possible mechanism Methods: The experiment was divided into aspirin pre-treatment part and ASA co-treatment with L-DOPA part.(1)ASA pre-treatment studies: 300 healthy male Sprague-Dawley(SD)rats(180-220 g)were divided into six groups as follows: Control group,ASA group,6-OHDA group,6-OHDA+ASA group,6-OHDA+L-DOPA group and 6-OHDA+ASA+L-DOPA group.Rats were received a single 6-hydroxydopamine(6-OHDA)8 ?g unilateral injection into the midbrain(substantia nigra pars compacta,SNc)through stereotaxic apparatus and sampled on the 7,14,21,28,35 and 42 days after 6-OHDA injected.The first 21 days,ASA group,6-OHDA+ASA group,and 6-OHDA+ASA+L-DOPA group were intragastriclly administrated with ASA(10 mg/kg)once a day,Control group and 6-OHDA group were administrated the same dose of normal saline.The last 21 days,ASA group,6-OHDA + ASA group,6-OHDA + L-DOPA group and 6-OHDA + ASA + L-DOPA group were intragastriclly administrated with ASA(10 mg/kg)or intraperitoneal injection of L-DOPA(25 mg/kg)once a day,Control group and 6-OHDA group were administrated the same dose of normal saline.(2)ASA co-treatment with L-DOPA studies: 84 male healthy SD rats(180-220 g)were divided into six groups as follows: Control group,ASA group,6-OHDA group,6-OHDA+ASA group,6-OHDA+L-DOPA group and 6-OHDA+L-DOPA+ASA group.Rats were received a single 6-OHDA unilateral injection into the midbrain SNc through stereotaxic apparatus and sampled on the 28 and 42 days after 6-OHDA injected.After 6-OHDA injected 21 days,ASA group,6-OHDA+ASA group,6-OHDA+L-DOPA group and 6-OHDA+ASA+L-DOPA group were intragastrically administered with ASA(10mg/kg)or L-DOPA(25mg/kg)intraperitoneally once a day,Control group and 6-OHDA group were given the same dose of normal saline.First,rats behavior change was detected by Rotarod test.Then,forepaw adjusting steps(FAS)test was used to investigated whether ASA affected L-DOPA efficacy and abnormal involuntary movements(AIM)test was used to analyse rats dyskinesias.In addition,The expressions of DA maker TH(DA neurons maker),IBA-1(microglia maker)and GFAP(astroglia markers)in midbrain were detected by immunohistochemistry,immunofluorescence and Western blot.The expressions of inflammatory factors COX-2,IL-6,iNOS in midbrain were detected by Western blot.Results: AIM scores showed that the rats AIM scores of the L-DOPA group significantly increased,ASA pre-treatment and ASA co-treatment with L-DOPA suppressed the development of dyskinesia.Rotarod test and FAS test showed that 6-OHDA decreased the time stayed on rod and forelimb steps,ASA pre-treatment and combined with L-DOPA improved 6-OHDA-induced rat behavior dysfunctions without affecting L-DOPA efficacy.In addition,6-OHDA caused rats DA neurons loss,glial cell activation,and inflammatory factor protein expression increased,but aspirin pre-treatment and ASA co-treatment with L-DOPA could ameliorated DA neuronal damage,decrease the activation of glial cell and the protein expression of COX-2,IL-6 and iNOS inflammatory mediators.Conclusion: These results suggest that ASA could inhibit the development of L-DOPA induce-dyskinesia,and its mechanism may be related to inhibit glia cell-mediated neuroinflammation.