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

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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 D1 receptor-binding assay using [3H]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 D1 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 D1 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.

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Acknowledgments

This work was supported by research grants from DBT, DST, ICMR, Govt. of India and KSCSTE, Govt. of Kerala to Dr. C. S. Paulose.

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  1. Molecular Neurobiology and Cell Biology Unit, Centre for Neuroscience, Department of Biotechnology, Cochin University of Science and Technology, Kochi, 682 022, Kerala, India

    M. S. Nandhu, E. T. Fabia & C. S. Paulose

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Correspondence to C. S. Paulose.

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Nandhu, M.S., Fabia, E.T. & Paulose, C.S. Dopamine D1 Receptor Gene Expression Studies in Unilateral 6-Hydroxydopamine-Lesioned Parkinson’s Rat: Effect of 5-HT, GABA, and Bone Marrow Cell Supplementation. J Mol Neurosci 41, 1–11 (2010). https://doi.org/10.1007/s12031-009-9213-8

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