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Elevated NMDA receptors in parkinsonian striatum
F B Weihmuller1, J Ulas, L Nguyen
1Department of Psychobiology, University of California, Irvine 92717.
Neuroreport
|November 1, 1992
Summary
Parkinson's disease (PD) is linked to reduced dopamine transporter levels in the striatum. This study found increased N-methyl-D-aspartate (NMDA) receptor binding in PD patients, suggesting altered glutamate signaling.
Area of Science:
- Neuroscience
- Neurology
- Biochemistry
Background:
- Dopamine-glutamate interactions are crucial for striatal function.
- Dysregulation of these interactions is implicated in neurotoxicity at dopamine terminals.
- Idiopathic Parkinson's disease (PD) involves nigrostriatal dopamine (DA) pathway degeneration.
Purpose of the Study:
- To investigate regional differences in dopamine transporter and N-methyl-D-aspartate (NMDA) receptor binding in the striata of PD patients.
- To explore the relationship between dopamine transporter levels and NMDA receptor activity in PD.
Main Methods:
- Utilized [3H]Mazindol to label dopamine transporters in post-mortem striatal tissue.
- Assessed L-[3H]glutamate binding to NMDA-sensitive receptors in PD patients and age-matched controls.
- Analyzed regional variations in binding within the caudate and putamen.
Main Results:
- Dopamine transporter levels were significantly reduced (70-80%) in the caudate and putamen of PD patients.
- Reductions in dopamine transporters were more pronounced in dorsal compared to ventral striatal regions.
- L-[3H]glutamate binding to NMDA-sensitive receptors was elevated by 20-40% in PD cases versus controls.
Conclusions:
- Findings suggest significant alterations in dopamine transporter availability and NMDA receptor binding in the striatum of PD patients.
- The observed changes may indicate modifications within corticostriatal glutamate synapses.
- These alterations could be a consequence of reduced nigrostriatal dopamine activity in Parkinson's disease.