Effects And Mechanism Of Uric Acid On Learning And Memory Ablility Of Rats With Parkinson's Disease

BackgroundParkinson's disease, occurs in the elderly, is a common degenerative disease of the central nervous system, oxidative stress is closely related with pathological deficiency of substantia nigra dopaminergic neurons in PD pathogenesis. The traditional symptom of PD is dyskinesia. Study showed that the selective dopaminergic neuron loss can lead to defects of cognitive function in rats and primates. Uric acid is an important physiological antioxidant, which has effects on anti-oxidative stress and protecting dopamine neurons. Recent studies showed that higher plasma concentrations of uric acid can reduce the incidence of PD, improve cognitive function and the prognosis of patients with PD, its internal mechanisms still need further research for future clinical application of uric acid to provide experimental basis.ObjectiveTo investigate the effects of uric acid upon learning and memory ability of Sprague-Dawley rat Parkinson's disease models induced by 6-OHDA and its mechanism.MethodsFemale SD rats were divided into control group (group A), PD group (group B), PD uric acid treatment group (group C1-C5),each group of 15.In the first 1～6day group C1l～C5 was intraperitoneally injected 0.1,1,5,10,20 mg/(kg·d) uric acid, groups A,B were intraperitoneally injected equal dose of normal saline.In the third week,each group were given Y-type electric maze test.In the fourth week all rats were decapitated, malondialdehyde(MDA) content in striatum was measured by using spectrophotometer, tyrosine hydroxylase (TH) and Caspase-3-positive neurons in substantia nigra were identified by immunohistochemistry.ResultsAverage learning achievement of group A was 4.12±1.57times, memory performance was 3.17±1.19 times. Compared with group A, learning and memory ability of group B and groups C1-C5 decreased significantly (P<0.01), in damaged side of the striatum MDA content increased, in the substantia nigra TH-positive cell counts decreased, Caspase-3-positive cell counts increased; Compared with group B, groups C2,C3,C4 significantly showed increased learning and memory ability(P<0.01), in damaged side of the striatum the MDA content decreased, in the substantia nigra TH-positive cell counts increased, Caspase-3 positive cell counts decreased, groups C1,C5 showed no difference(P>0.01); between groups C2,C3 and group C4 there was significant difference(P<0.01).ConclusionsLearning and memory ability in PD rats was significantly decreased, while appropriate doses of uric acid can improve the PD learning and memory ability, and the mechanism may be related to its neuroprotective property by reducing the oxidative stress to decrease dopaminergic neuronal apoptosis,thus to protect the dopaminergic neurons.