Dopaminergic Neurons in the Substantia Nigra in Normal Aging and MPTP-Lesioned Mice

Abstract

Parkinson’s disease is a slowly progressive neurodegenerative disorder that seldom occurs in patients below the age of 60. Its incidence increases with age, but the cause remains unknown. Typically, the disease is characterized by decreased dopamine levels in the striatum and a loss of pigmented dopamine nerve cells in the substantia nigra pars compacta. 1-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is a commercially available compound that has been illicitly used as a new type of heroin (Langston et al, 1983). Many users developed a Parkinson-like disorder with bradykinesia, rigidity, tremor, flexed posture, loss of postural reflexes, mutism, and drooling following intravenous (IV) administration of MPTP (Davis et al., 1979; Langston et al., 1983; Langston and Ballard, 1985). Since then, MPTP has been shown to produce parkinsonian symptoms and neuropathology of the nigrostriatal dopamine system in nonhuman primates as well as in mice (Burns et al., 1983; Langston et al., 1985; Heikkila et al., 1984; Gupta et al., 1984–1986).