Targeted toxicants to dopaminergic neuronal cell death

Parkinson's disease (PD ) is mainly characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra resulting in chronic deficits in motor functions. Administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP ) produces PD symptoms and recapitulates the main features of PD in human and animal models. MPTP is converted to 1-methyl-4-phenylpyridine (MPP+ ), which is the active toxic compound that selectively destroys dopaminergic neurons. Here, we describe methods and protocols to evaluate MPTP/MPP+-induced dopaminergic neurodegeneration in both murine primary mesencephalic cultures and animal models. The ability of MPTP/MPP+ to cause dopaminergic neuronal cell death is assessed by immunostaining of tyrosine hydroxylase (TH).