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Publication Detail

Title: Protease-activated receptor-1 mediates protection elicited by thrombin preconditioning in a rat 6-hydroxydopamine model of Parkinson's disease.

Authors: Cannon, Jason R; Keep, Richard F; Schallert, Timothy; Hua, Ya; Richardson, Rudy J; Xi, Guohua

Published In Brain Res, (2006 Oct 20)

Abstract: The etiology of Parkinson's disease remains poorly understood, and current treatment options do not slow disease progression. Recently, chemical (thrombin) preconditioning (TPC) was found to be protective in a 6-hydroxydopamine (6-OHDA) model of the disease. It is important to understand the mechanisms behind these thrombin-induced protective effects. The current study was conducted in the rat to determine whether the protective effects of TPC are mediated via activation of protease-activated receptors (PARs). Preconditioning with specific local infusion of agonist peptides for PAR-1 and PAR-4 3 days before unilateral 6-OHDA administration (10 microg into the medial forebrain bundle) was tested. In addition, co-administration of a PAR-1 antagonist with TPC was examined. In a neurobehavioral assessment battery, PAR-1 agonist preconditioning provided protection in a vibrissae-elicited forelimb placing test, a forelimb-use asymmetry test, and a corner turn test. In addition, inclusion of a PAR-1 antagonist prevented the protective effects elicited by TPC. In contrast to the effects of the PAR-1 agonist, PAR-4 agonist preconditioning afforded no such protection. Indeed, in a lower-dose model of 6-OHDA (5 microg), PAR-4 preconditioning significantly increased behavioral deficits. These results indicate that the protective effects of TPC in this model are mediated through PAR-1 activation. Neither the effects of PAR-1 nor TPC on later 6-OHDA-induced behavioral deficits appeared to be mediated through (DA) content sparing. Further mechanistic studies on the actions of PAR-1 and PAR-4 as detrimental in experimental models of Parkinson's disease are warranted.

PubMed ID: 16934779 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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