Accession Number:

ADA415837

Title:

Metabotropic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease

Descriptive Note:

Final rept. 24 Sep 1998-23 Sep 2002

Corporate Author:

EMORY UNIV ATLANTA GA

Personal Author(s):

Report Date:

2002-10-01

Pagination or Media Count:

213.0

Abstract:

In Parkinsons 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, 23, 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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE