Metabotropic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease
Abstract
Parkinson's disease (PD) is characterized by a loss of substantia nigra dopaminergic neurons. Here we describe our progress in understanding the role of metabotropic glutamate receptors (mGluRs) as a novel target for the treatment of PD. We have localized mGluR4 in basal ganglia structures, and explored its role in mediating the electrophysiological effects of glutamate in rat brain slices. We have explored the efficacy of mGluR drugs in relieving motor symptoms in hemiparkinsonian monkeys. We found that group III mGluRs are presynaptic on striatal-pallidal terminals and that they mediate a reduction in IPSC amplitude in the SNr. They also pre-synaptically inhibit EPSCs at the STN-SNr synapse. In this study, we have found that groups I and II mGluRs also have critical roles in regulating basal ganglia function. Group II mGluRs mediate a presynaptic reduction of EPSCs in the SNr and group II agonist LY354740 reverses catalepsy in a rodent model of PD. Pre- and Post-synaptic group I mGluRs are involved in regulation of basal ganglia output nuclei by both excitation and disinhibition. Furthermore, comprehensive characterization of the roles of mGluRs in the basal ganglia raises the possibility that they may provide targets for novel therapeutic agents for treatment of PD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2001
- Accession Number
- ADA405511
Entities
People
- Allan I. Levey
Organizations
- Emory University