Parkinson's Disease
Volume 2010 (2010), Article ID 190450, 12 pages
doi:10.4061/2010/190450
Research Article
Neuroprotection and Functional Recovery Associated with Decreased Microglial Activation Following Selective Activation of mGluR2/3 Receptors in a Rodent Model of Parkinson's Disease
1Parkinson's Disease Research Group, Faculty of Medicine, Imperial College London, 4th Floor, Burlington Danes Building, Hammersmith Hospital, Du Cane Road, W12 0NN London, UK
2Centre for the Cellular Basis of Behaviour, Department of Neuroscience, Institute of Psychiatry, Kings College London, 1st Floor, The James Black Centre, Coldharbour Lane, SE5 9NU London, UK
Received 16 January 2010; Revised 24 February 2010; Accepted 8 March 2010
Academic Editor: Antonio Pisani
Copyright © 2010 Hugh Chan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Clinical trials have demonstrated positive proof of efficacy of dual metabotropic glutamate receptor 2/3 (mGluR2/3) agonists in both anxiety and schizophrenia. Importantly, evidence suggests that these drugs may also be neuroprotective against glutamate excitotoxicity, implicated in the pathogenesis of Parkinson's disease (PD). However, whether this neuroprotection also translates into functional recovery is unclear. In the current study, we examined the neuroprotective efficacy of the dual mGluR2/3 agonist, 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), and whether this is accompanied by behavioral recovery in a rodent 6-hydroxydopamine (6-OHDA) model of PD. We now report that delayed post lesion treatment with 2R,4R-APDC (10 nmol), results in robust neuroprotection of the nigrostriatal system, which translated into functional recovery as measured by improved forelimb use asymmetry and reduced (+)-amphetamine-induced rotation compared to vehicle treated animals. Interestingly, these beneficial effects were associated with a decrease in microglial markers in the SNc, which may suggest an antiinflammatory action of this drug.