Levodopa response motor complications--GABA receptors and preproenkephalin expression in human brain.
Post-mortem studies in human brain of patients with Parkinson's disease have greatly contributed to our understanding of the disease. However, few human brain studies have focused on levodopa-induced dyskinesias, which considerably limit the beneficial effect of levodopa (LD) in the treatment of Parkinson's disease. We have taken advantage of the fact that some patients develop dyskinesias and other do not to compare biochemical markers between them. In post-mortem samples from LD-treated parkinsonian patients, increased preproenkephalin expression in the putamen and increased GABA(A) receptors content in the internal globus pallidus (GPi) are found in dyskinetic parkinsonian patients compared to non-dyskinetic patients. These data are consistent with previous observations in MPTP monkeys developing dyskinesias following LD or dopamine agonist treatment. This combination of data in an animal model and in humans strongly suggests that increased enkephalinergic activity in the putamen and increased sensitivity of GABA(A) receptors in the GPi are implicated in the pathogenesis of LD-induced dyskinesias in Parkinson's disease.
Calon
Frédéric
F
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, Pavillon CHUL, CHUQ, 2705, Laurier Boulevard, G1V 4G2, Sainte-Foy, Que, Canada.
Di Paolo
Thérèse
T
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000473:pathology; D004745:Enkephalins / Q000096:biosynthesis*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D011498:Protein Precursors / Q000096:biosynthesis*; D018079:Receptors, GABA / Q000096:biosynthesis*
D004745:Enkephalins; D011498:Protein Precursors; D018079:Receptors, GABA; D007980:Levodopa; C033660:preproenkephalin