Altered expression of calcium- and apoptosis-regulating proteins in multiple system atrophy Purkinje cells

The expression patterns of the calcium binding proteins calbindin and parva lbumin and of the apoptosis modulating proteins Bcl-2, Bar, and Bcl-x were studied in the cerebellum of patients with multiple system atrophy (MSA). C albindin and parvalbumin immunoreactivity was markedly decreased in MSA Pur kinje cells whereas Bar and Bcl-x protein expression was increased. Bcl-2 e xpression was restricted to a subpopulation of granule neurons, but no decr ease of Bcl-2 was evident in MSA. Additional DNA end-labeling (ISEL) studie s revealed only one possible apoptotic Purkinje cell nucleus, but nuclei in the cerebellar white matter, probably oligodendrocytes, in the cerebellum of patients with MSA. The present results suggest that a diminished calcium binding capacity of MSA Purkinje cells might lead to a change in the regul ation of proteins of the bcl-2 family that could favor the pathologic initi ation of apoptosis.