NEUROPROTECTIVE EFFECTS OF P2X4 RECEPTOR ON 6-OHDA-INDUCED PARKINSON'S DISEASE IN RATS

Yonghong Yang^{1, #}, Liang Zhou^{2, #}, Baike Zhu³, Yong Wang⁴, Liming Chen⁵, Chao Wang², Yingchun Meng², Ke Han^{2, *}

¹Department of Neurology, The fifith hospital of Jinan, Jinan, PR China - ²Department of Rehabilitation Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China - ³Department of Neurology, Shandong Provincial Third Hospital, Jinan, PR China - ⁴Department of Tuina, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China - ⁵Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China

Objective: To investigate the neuroprotective mechanism and effect of P2X4 receptor (P2X4R) inhibition on 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease in rats. 

Methods: Seventy-two clean, healthy male Wistar rats were randomly selected, and 6-OHDA was used to establish a rat model of Parkinson’s disease. The rats were divided into control group, model group and intervention group, with 24 rats in each group. The number of tyrosine hydroxylase-positive neurons was calculated by fluorescence microscopy. The mRNA and protein expression levels of P2X4R, interleukin-18 (IL-18), interleukin-1β (IL-1β), caspase-1 and NLRP3 in the substantia nigra of each group were determined by real-time fluorescence quantitative PCR. 

Results: The number of tyrosine hydroxylase-positive neurons in the model group was significantly decreased compared to the control group, and the mRNA and protein expression levels of P2X4R, IL-18, IL-1β, caspase-1 and NLRP3 in the substantia nigra were significantly increased (P<0.05). Compared with the model group, the number of tyrosine hydroxylase positive neurons in the intervention group was significantly increased, and the mRNA and protein expression levels of P2X4R, IL-18, IL-1β, caspase-1 and NLRP3 in the substantia nigra were significantly decreased (P<0.05).

Conclusion: Inhibition of P2X4R has a neuroprotective effect on 6-OHDA-induced Parkinson’s disease, which may be a result of inhibiting the inflammatory response and reducing the degeneration and death of tyrosine hydroxylase-positive dopaminergic neurons in the substantia nigra of Parkinson’s rats.