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Neuroprotective effect of l‐dopa on dopaminergic neurons is comparable to pramipexol in MPTP‐treated animal model of Parkinson’s disease: a direct comparison study

Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by selective loss of dopaminergic neurons in the pars compacta of the substantia nigra. Levodopa (l‐dopa) and dopamine agonists have been most commonly used for symptomatic treatment. However, there are discrepancies between clinical and experimental data with respect to the neuroprotective effects of these drugs on dopaminergic neurons. In this study, to determine whether l‐dopa is toxic or dopamine agonist is neuroprotective to dopaminergic neurons, we evaluated the neuroprotective properties of l‐dopa and the pramipexol (PPX), one of dopamine agonists, with a focus on the regulatory effects of the anti‐oxidant properties and cell survival or apoptotic signal pathways in the same experimental design, using 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated PD animals. The glutathione level in MPTP‐treated mice was significantly increased by PPX administration but not by L‐dopa treatment. The expression of phosphorylated extracellular signal regulated kinase in MPTP‐treated mice was significantly increased only with l‐dopa treatment. Treatment with either l‐dopa or PPX in MPTP‐treated mice led to significantly decreased expressions of JNK phosphorylation, Bax, and cytochrome c and to an increased level of Bcl‐2 expression with a similar degree, compared with the levels in MPTP‐only treated mice. Immunohistochemical analysis showed that both l‐dopa and PPX increased significantly survival of dopaminergic neurons in MPTP‐treated mice. Our study demonstrated that both l‐dopa and PPX had comparable neuroprotective properties for dopaminergic neurons in MPTP‐treated PD animal models, through modulation of cell survival and apoptotic pathways.