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 anda 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.