Study On Cognitive Impairment And Tau Protein Phosphorylation In MPTP-induced Parkinson Model Mice

Part1Study on cognitive impairment in MPTP-induced Parkinson model micePurpose:We’ll research on cognitive impairment in subacute and chronicMPTP-induced Parkinson model mice.Methods:This study made subacute and chronic Parkinson model C57BL/6mice by intraperitoneal injection of MPTP25mg/kg/day for5consecutive days and25mg/kg/3.5days for10times, respectively. Dynamic observe a variety of neurological behaviors and cognitive behaviors, to explore movement and cognitive disorders of each model. Use immunohistochemical methods to understand substantia nigra tyrosine hydroxylase (TH) staining neurons change caused by MPTP.Results:Compared with the control group, results in pole test and grid test were significantly difference in the experimental group of subacute model mice, but symptoms gradually recovered; There were no significante different when tested in3w and7w time points repeatedly; latencies was prolonged significantly in2w time point in Cued Morris water maze task; latencies were significantly prolonged in4w time point in passive avoidance test; immunohistochemistry showed that TH-positive cells in substantial nigra decreased, gradually restored with time, damage less than50%in2w time point.Conclusions:1. there were dyskinesia in both MPTP-induced subacute and chronic Parkinson model mice. Dyskinesia in subacute model got recovery with time while in chronic model lasted longer, which consistent with TH-positive cells changes.2. There was cognitive impairment in MPTP-induced subacute and chronic Parkinson model mice. Part2Study on Tau protein phosphorylation in MPTP-induced Parkinson model miceObjective:To observe the Tau protein changes in MPTP-induced subacute and chronic Parkinson mice model with cognitive impairment.Methods:using western blot method to test total tau protein and phosphorylated tau protein changes in brain tissue (striatum, black mass, hippocampus, prefrontal cortex) in different groups; observe them in different time points to see the change tendcy in two models.Results:Total tau protein had no significant differernce and phosphorylated tau protein (at Ser262, Ser214, Ser396/404) increased in both subacute and chronic MPTP-induced Parkinson model mice. Phosphorylated tau protein level at Thr205had no significant increase. phosphorylation level in striatum was the highest in two models1W after modeling; phosphorylation levels in prefrontal cortex, hippocampus, striatum, substantia nigra were at the highest level1W or2W after modeling in subacute model mice experimental group, with time increased rapidly decline; phosphorylation level in substantia nigra increased slowly in chronic model experimental group1W after modeling; while rapidly in striatum, but lower than the experimental group of subacute model; phosphorylation levels in striatum, substantia nigra were at the highest level1W or2W after modeling in chronic model mice experimental group; phosphorylation levels in prefrontal cortex, hippocampus were slowly growth, reaching peak time later than in substantia nigra and striatum; overall phosphorylation levels in chronic model experimental group were less than that in subacute model experimental group, but decline slowly.Conclusions:cognitive impairment in subacute and chronic MPTP-induced Parkinson model mice may be related to phosphorylated tau protein.