Abstract
Parkinson's disease is characterized by progressive cell death in the substantia nigra pars compacta, which leads to dopamine depletion in the striatum and indirectly to cortical dysfunction. Increased glutamatergic transmission in the basal ganglia is implicated in the pathophysiology of Parkinson's disease and glutamate receptor mediated excitotoxicity has been suggested to be one of the possible causes of the neuronal degeneration. In the present study, the effects of serotonin, gamma-aminobutyric acid and bone marrow cells infused intranigrally to substantia nigra individually and in combination on unilateral 6-hydroxydopamine induced Parkinson's rat model was analyzed. Scatchard analysis of total glutamate and NMDA receptor binding parameters showed a significant increase in Bmax (P < 0.001) in the cerebral cortex of 6-hydroxydopamine infused rat compared to control. Real Time PCR amplification of NMDA2B, mGluR5, bax, and ubiquitin carboxy-terminal hydrolase were up regulated in cerebral cortex of 6-hydroxydopamine infused rats compared to control. Gene expression studies of GLAST, ά-Synuclien and Cyclic AMP response element-binding protein showed a significant (P < 0.001) down regulation in 6-OHDA infused rats compared to control. Behavioural studies were carried out to confirm the biochemical and molecular studies. Serotonin and GABA along with bone marrow cells in combination showed reversal of glutamate receptors and behaviour abnormality shown in the Parkinson's rat model. The therapeutic significance in Parkinson's disease is of prominence.
Highlights
Parkinson’s disease (PD), one of the most prevalent neurodegenerative disorders among the elderly population, is charecterised by dopamine neurons degeneration in the substantia nigra pars compacta
We have previously shown that Serotonin (5HT) and Gamma aminobutyric acid (GABA) acting through specific receptor subtypes 5HT2 [16] and GABAA [17] respectively, control cell proliferation and act as comitogens
Dopamine content in the cerebral cortex 6-OHDA infusion in to the Substantia nigra Pars compacta (SNpc) resulted in a significant (p < 0.001) decrease in dopamine content in the cerebral cortex of PD rats
Summary
Parkinson’s disease (PD), one of the most prevalent neurodegenerative disorders among the elderly population, is charecterised by dopamine neurons degeneration in the substantia nigra pars compacta. Autologous bone marrow cells (BMC) can be used as a source of progenitor cells for the central nervous system. It circumvents both ethical and immunological constraints related with stem cell therapy. Lauder and Krebs [10] reported that parachlorophenylalanine (PCPA), a 5-HT synthesis inhibitor, retarded neuronal maturation, while mild stress, a releaser of hormones, accelerated neuronal differentiation. These workers defined differentiation as the cessation of cell division measured by incorporation of 3H-thymidine. GABA was demonstrated as acting as a chemoattractant and being involved in the regulation of progenitor cell proliferation. Our present study demonstrates the structural and molecular changes of 6-OHDA infused unilateral Parkinson’s model using 5-HT, GABA and BMC individually and in combination
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