Neuroprotective Effect of Curcumin on the Nigrostriatal Pathway in a 6-Hydroxydopmine-Induced Rat Model of Parkinson's Disease is Mediated by alpha 7-Nicotinic Receptors

Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by selective degeneration of dopaminergic nigrostriatal neurons. Most of the existing pharmacological approaches in PD consider replenishing striatal dopamine. It has been reported that activation of the cholinergic system has neuroprotective effects on dopaminergic neurons, and human alpha 7-nicotinic acetylcholine receptor (alpha 7-nAChR) stimulation may offer a potential therapeutic approach in PD. Our recent in-vitro studies demonstrated that curcumin causes significant potentiation of the function of alpha 7-nAChRs expressed in Xenopus oocytes. In this study, we conducted in vivo experiments to assess the role of the alpha 7-nAChR on the protective effects of curcumin in an animal model of PD. Intra-striatal injection of 6-hydroxydopmine (6-OHDA) was used to induce Parkinsonism in rats. Our results demonstrated that intragastric curcumin treatment (200 mg/kg) significantly improved the abnormal motor behavior and offered neuroprotection against the reduction of dopaminergic neurons, as determined by tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra and caudoputamen. The intraperitoneal administration of the alpha 7-nAChR-selective antagonist methyllycaconitine (1 mu g/kg) reversed the neuroprotective effects of curcumin in terms of both animal behavior and TH immunoreactivity. In conclusion, this study demonstrates that curcumin has a neuroprotective effect in a 6-hydroxydopmine (6-OHDA) rat model of PD via an alpha 7-nAChR-mediated mechanism.