Dopamine D1 Receptor Gene Expression Studies in Unilateral 6-Hydroxydopamine-Lesioned Parkinson’s Rat: Effect of 5-HT, GABA, and Bone Marrow Cell Supplementation

Abstract

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.