Neuroprotective Effect of Curcumin on the Rat Model of Parkinson's Disease Induced by Rotenone via Modulating Tyrosine Hydroxylase and Dopa Decarboxylase Expression Levels

Parkinson's disease is a progressive neurodegenerative disorder distinguished by degeneration of dopaminergic neuronal cells of the substantia nigra pars compacta (SNpc) in the midbrain. Tyrosine hydroxylase (TH) and Dopa decarboxylase (DDC) are key players in the dopamine synthesis pathway. Curcumin (CUR), a polyphenolic compound, has therapeutic properties against broad spectrum neurodegenerative diseases. In this work, we evaluated the potential protective effect of CUR in a rat model of PD. Adult male rats were orally treated with rotenone (ROT) (2.5 mg/kg/day) with or without CUR (200 mg/kg/day) for 5 consecutive weeks. Oxidative stress (malondialdehyde, MDA; nitric oxide, NO; acetylcholine esterase, AchE; reduced glutathione, GSH) and antioxidant biomarkers (superoxide dismutase, SOD; catalase, CAT), neurochemicals (dopamine; DA and L-DOPA) concentrations, the expression levels of TH and DDC, and histopathological investigations were carried out. ROT-treated rats showed a significant increase in the levels of MDA, NO and an increased activity of AchE. A significant decrease in the level of GSH and in the activities of SOD and CAT and the levels of DA and L-DOPA was observed when compared to controls. The mRNA expression levels of DDC in ROT-treated animals were significantly elevated compared to controls. At the tissue level, SNpc sections from ROT-treated animals were characterized by severe neuronal damage. Treatment with CUR and ROT remarkably alleviated all the aforementioned ROT-induced effects. In conclusion, CUR showed promising neuroprotective actions in ROT-induced PD through inhibiting oxidative stress, activation of the antioxidant system, modulating the neurotransmitters imbalance and the genetic expression of TH and DDC.