Title

 

Authors

S. del C. Bastias Candia

Doctorate School in Pharmacology and Toxicology
Dept. of Pharmacology – University of Bologna, Italy

 

Abstract

Parkinson’s disease (PD) is a chronic progressive neurodegenerative disorder of movement of likely multi-factorial origin. A significant genetic component in the aetiology of PD is suggested [1] and, in addition, environmental toxins such 6-OHDA [2] and MPTP [3] as well as agricultural chemicals like Rotenone, Paraquat (PQ) and Maneb (MB) [4,5] have been associated with PD. The aim of this study is to investigate the possible role of N/OFQ-NOP system in the pathogenesis of the disease in an animal model developed using PQ and/or MB. Adult male Sprague–Dawley rats were used, injected intraperitoneally (i.p.) twice a week for 4 weeks (total of 8 injections) with saline solution (vehicle, n = 10), PQ (10 mg/kg, n = 10), MB (30 mg/kg, n = 10), PQ + MB (10 + 30 mg/kg, n = 10) and  PQ + MB (5 + 15 mg/kg, n = 10). Doses have been chosen based on previously reports [6,7]. Weight, locomotion activity and specific behaviours of the animals have been registered daily. We determined the levels of tyrosine hydroxylase (TH), the rate-limiting enzyme for DA synthesis,in the substantia nigra (SN), using Western analysis.  Quantification of nociceptin system genes expression in SN of all animals treated was performed by RT-PCR techniques. All treated animals began to lose weight and some animals died after the 3rd injections of PQ + MB high dose (10 + 30 mg/kg) and after the 5th injection of PQ (10 mg/kg) showing clear signs of sufering. The locomotion activity decrease evidently but not significantly in treated animals compared with control group and the animal behavior show a significant difference between the PQ, PQ+ MB groups with the control group. A decrease of TH immunoreactivity was observed in all animals treated except for MB. The Nociceptin/orphanin FQ (N/OFQ) gene expression showed an increase versus control group, whereas it was possible to observe a statistically significant decrease in NOP receptor mRNA. Moreover, these data strengthen the hypothesis that this neuropeptidergic system could be implicated in the mechanisms underlying Parkinson's disease.
 
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