Striatal dopamine- and glutamate-mediated dysregulation in experimental parkinsonism.
Characteristic changes involving interactions between dopamine and glutamate in striatal medium spiny neurons now appear to contribute to symptom production in Parkinson's disease (PD). The balance between kinase and phosphatase signaling modifies the phosphorylation state of glutamate receptors and thus their synaptic strength. Sensitization of spiny-neuron NMDA and AMPA receptors alters cortical glutamatergic input to the striatum and modifies striatal GABAergic output, and thus motor function. Conceivably, the pharmacological targeting of spiny-neuron mechanisms modified in PD will provide a safer and more effective therapy.
Chase
T N
TN
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
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JD
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology*; D008959:Models, Neurological; D009476:Neurons, Efferent / Q000378:metabolism* / Q000648:ultrastructure; D020734:Parkinsonian Disorders / Q000378:metabolism*; D010770:Phosphotransferases / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction
D000978:Antiparkinson Agents; D011954:Receptors, Dopamine; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D007980:Levodopa; D010770:Phosphotransferases; D004298:Dopamine