Metabotrobic Glutamate Receptor mGluR4 as a Novel Target for Parkinson's Disease.
Annual rept. 24 Sep 98-23 Sep 99
EMORY UNIV ATLANTA GA
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The symptoms of Parkinsons disease PD are associated with a loss of substantia nigra dopaminergic neurons involved in modulation of function of the basal ganglia BG . This report describes our progress in understanding the role of metabotropic glutamate receptors mGluRs as a novel target for the treatment of PD. Specifically, our aims are to localize mGluR4 in rat and monkey basal ganglia structures, to determine the role of this receptor vs. other subtypes in mediating the electrophysiological effects of glutamate in rat brain slices, and to determine the efficacy of drugs aimed mGluRs 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. Group III mGluRs also presynaptically inhibit EPSCs at the STN-SNr synapse. Group II mGluRs were found to mediate a presynaptic reduction of EPSCs in the SNr and group II agonist LY354740 reverses catalepsy in an animal model of PD. Furthermore, as these studies progress, the distribution and physiological roles of mGluRs in the BG raises the possibility that these receptors may provide targets for novel therapeutic agents for treatment of PD and related disorders.
- Medicine and Medical Research
- Stress Physiology