Metabotropic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease
Abstract
In Parkinson's disease (PD) nigrostriatal dopaminergic neurons selectively die. Here we describe our contributions toward understanding basal ganglia (BG) function and the suitability of metabotropic glutamate receptors (mGluRs) as targets for treating PD. We employed immunocytochemistry to describe the anatomical localization of mGluRs 4, 2/3, la, and 5 in BG nuclei. We used electrophysiology to describe how mGluRs mediate the effects of glutamate in rat brain slices. We tested the efficacy of mGluR drugs in relieving motor symptoms in hemi-parkinsonian monkeys, a non-human primate model of PD. We found that group III mGluRs are presynaptic on striatal-pallidal terminals and they reduce IPSO amplitude in the SNr. They also pre-synaptically inhibit EPSOs at the STN-SNr synapse. Groups I and II mGluRs also regulate BG function. Group II mGluRs mediate a presynaptic reduction of EPSOs in the SNr and group II agonist LY35474O reverses catalepsy in (a rodent) model of PD. Post-synaptic group I mGluRs regulate BG output nuclei by both excitation and disinhibition, and are enriched in the globus pallidus. Furthermore, the limited availability of orally available mGluR drugs confounds our ability to ascertain wheter mGluRs will remain a viable target for the treatment of PD in humans.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2002
- Accession Number
- ADA415837
Entities
People
- Allan I. Levey
Organizations
- Emory University