Dopamine D1 receptor gene expression studies in unilateral 6-hydroxydopamine-lesioned Parkinson's rat: effect of 5-HT, GABA, and bone marrow cell supplementation.
Parkinson's disease is the second most common neurodegenerative disorder and remains incurable. Many potential compensatory mechanisms have now been proposed; these are both dopaminergic, focused on enhancing effects or exposure to existing dopamine, and non-dopaminergic, being focused on reducing activity of the indirect striatal output pathway. In the present study, the effects of serotonin, gamma-aminobutyric acid, and bone marrow cell supplementation intranigrally to the substantia nigra on unilateral 6-hydroxydopamine-infused rats were analyzed individually. Dopaminergic binding parameters were done by Scatchard analysis of dopamine D(1) receptor-binding assay using [(3)H]SCH 23390. In the corpus striatum, 6-hydroxydopamine-infused rats showed a significant decrease in B (max) (P < 0.001), and in cerebral cortex, they showed a significant increase in B (max) (P < 0.001) compared to control. Real-time polymerase chain reaction amplification of dopamine D(1) was downregulated (P < 0.001) in the corpus striatum of 6-hydroxydopamine-infused rats compared to control, whereas in the cerebral cortex, it showed a significant upregulation (P < 0.001). Behavioral studies were carried out to confirm the biochemical and molecular studies. Serotonin and gamma-aminobutyric acid supplementation reversed these changes to control. The bone marrow cell-treated group of our studies does not show much significant change as compared to the serotonin and gamma-aminobutyric acid-supplemented groups. The alterations in dopamine D(1) receptor-binding parameters and gene expression during Parkinson's model were reversed by serotonin and gamma-aminobutyric acid supplementation in our experiments, which has clinical significance in the management of the disease.
Nandhu
M S
MS
Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Kochi, 682 022, Kerala, India.
Fabia
E T
ET
Paulose
C S
CS
D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D016026:Bone Marrow Transplantation; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008297:Male; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018663:Adrenergic Agents; D017447:Receptors, Dopamine D1; D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D004298:Dopamine