Curcumin Prevents and Ameliorates Biochemical and Behavioral Toxicities of MPTP in C57BL/6J Mice: Its Potential use in Preventing and Treating Parkinsonism

Parkinson's disease (PD) is the result of the degeneration of nigrostriatal dopamine neurons and loss of striatal tyrosine hydroxylase and dopamine.The cause is unknown.Studies have shown that fetal exposures to toxins make the nigrostriatal dopamine neurons vulnerable and that later toxic challenges and/or the wear-and-tear of aging cause the already vulnerable neurons to succumb, and producing a model of parkinsonism.Thus, a sensitization stage and a precipitating stage may exist for idiopathic PD.In this study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to produce the proposed sensitization and precipitating stages and determine if curcumin can ameliorate the toxic changes.Note: however that MPTP serves as a protoxin, via it metabolism by monoamine axidase B (MAO-B) to 1-methyl-4-phenylpyridinium (MPP+).MPP+ has affinity for the catecholamine uptake system, is taken up preferentially into dopaminergic neurons with cell bodies in the substantia nigra zona compacta, where it inhibits complex-1 of the electron transport chain.C57BL/6J pregnant mice were treated with low dosage of MPTP during gestation days (GD) 8-12, to cause sub-threshold impairments to the emerging and vulnerable nigrostriatal dopamine neurons in the fetus, thus producing phenotypic sensitization.At 3 months, the offspring of the PBS control and the MPTP group were challenged with PBS or MPTP (10 mg/kg/day) for seven days, to cause further harm and to the produce the precipitating stage.The ameliorating effect of curcumim was tested on both stages, by pretreating with 15 µg/animal during GD 3-12.All animals were studied for motor activities, the levels of TH, and dopamine and its metabolites.The prenatal treatments with curcumin nullify the reduction in birth weight caused by prenatal MPTP, and it blocked the impairments in movement caused by prenatal MPTP, postnatal MPTP and combination of prenatal and postnatal MPTP.Curcumin also restored dopamine to 97.3% from the 47.2% loss caused by prenatal MPTP, and to 68.7% from the 32.8% loss caused by the prenatal and postnatal MPTP treatments.TH expression was also markedly restored.These novel data show the efficacy of curcumin and suggest that the curcumin may be valuable in preventing and ameliorate PD-like changes.