Melanin, tyrosine hydroxylase, calbindin and substance P in the human midbrain and substantia nigra in relation to nigrostriatal projections and differential neuronal susceptibility in Parkinson's disease

Abstract

The anatomy of melanin-containing neurons and other midbrain structures was examined by tyrosine hydroxylase (TH), calbindin D 28k, and substance P immunostaining. Greater than 95% of cells in the substantia nigra pars compacta contained melanin, but densely packed cells in a ventral tier had a low content of melanin and loosely packed cells in a dorsal tier had a high content of melanin. Approximately 60% in the γ group and 40% in the retrorubal nucleus had a low content of melanin. TH immunostaining was moderate in both the ventral and dorsal tiers, but more intense in the γ group and retrorubral nucleus. Calbindin D 28k was absent from the ventral and dorsal tiers, but present in the γ group and retrorubral nucleus. In the light of primate tracing studies these findings suggest that the ventral tier of the pars compacta projects to striosomes of the striatum and the dorsal tier, γ group and retrorubral nucleus to the matrix compartment. The ventral tier is more vulnerable than the dorsal tier in Parkinson's disease, but the cells contain less melanin. Neither tier contains calbindin D 28k. This differential vulnerability between the ventral and dorsal tiers cannot be explained by melanin or calbindin D 28k.