Neuroprotection by urate on 6‐OHDA‐lesioned rat model of Parkinson's disease: linking to Akt/GSK3β signaling pathway

摘要: Higher plasma urate level is reported to be associated with a reduced risk and slower progression of Parkinson's disease (PD). In this study, we explored the effects on dopaminergic neurons in nigrostriatal pathway 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats. Uric acid (UA), when given twice daily at 200 mg/kg intraperitoneally for 10 consecutive days, elevated (the anionic form UA) striatum by 55% 36.8%, respectively, as compared vehicle group. This regimen UA was found ameliorate behavioral deficits, neuron loss well dopamine depletion system. Moreover, administration capable increasing glutathione superoxide dismutase activity while decreasing malondialdehyde accumulation striatum. addition, phosphorylation both protein kinase B (Akt) glycogen synthase 3 beta (GSK3β) striata 6-OHDA-lesioned rats dramatically sham-operated reduction attenuated Parkinsonian receiving treatment. Similarly, vitro findings showed that alleviated decrease Akt activation increase GSK3β caused 6-OHDA. Furthermore, neuroprotection its regulation Ser9 abolished presence PI3K inhibitor. Therefore, our demonstrated able protect rat against neurotoxicity 6-OHDA, beneficial may related Akt/GSK3β signaling.