Changes of melatonin and melatonin receptors on 6-OHDA induced Parkinson's disease in rat

Abstract

Objective To observe the changes of dopamine and its metabolites, melatonin, as well as melatonin receptors in the substantia nigras (SN) in 6-OHDA induced hemiparkinsonian rats. Methods PD rat was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta and medial forebrain bundle. Rats were divided into PD groups and vehicle groups, and sacrificed at 10∶00 and 22∶00 respectively, at 3 and 6 weeks post-lesion. The contents of dopamine and its metabolites as well as melatonin were measured by HPLC. The expressions of MT1 and MT2 mRNA and protein were detected by RT-PCR and Western-Blot respectively. Results Dopamine levels declined by 83% and 88% respectively at 3 and 6 weeks post-lesion in the injected side of PD rats, compared with the contralateral side. Melatonin levels in the injected side increased by 22% and 29% respectively. However, melatonin increased by 46% and 31% respectively at 10∶00 and 22∶00, at 6 weeks post-lesion in the contralateral side, compared with the same side of the vehicle. The expressions of MT1 and MT2 receptors mRNA were significantly decreased by 91.04% and 90.24% respectively in comparison with the vehicle, while the protein expression of MT1 and MT2 receptors significantly declined by 58% and 70% respectively. Conclusion Increased melatonin and down-regulated MT1 and MT2 receptors in the lesioned SN in 6-OHDA-induced rats may be associated with the progression of PD. Key words: Parkinson’s disease; Melatonin; Melatonin receptors