Metabotrobic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease
Abstract
Parkinson' S disease (PD) is characterized by a loss of substantial 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 mGluP4 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 mGluP drugs in relieving motor symptoms in hemi- parkinsonian 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 LY35474O reverses catalepsy in (a rodent) model of PD. Post-synaptic Group I mGluRs are involved in regulation of BG 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, 2000
- Accession Number
- ADA388425
Entities
People
- Alan I. Levey
Organizations
- Emory University