NEURAL HEME OXYGENASE-1 EXPRESSION IN IDIOPATHIC PARKINSONS-DISEASE

Heme oxygenase-l is a cellular stress protein expressed in brain and o ther tissues in response to oxidative challenge and other noxious stim uli. In the present study, immunohistochemistry was used to assess HO- 1 expression in various postmortem human brain specimens derived from PD and control subjects. In the substantia nigra of both PD and contro l specimens, moderate HO-1 immunoreactivity was consistently observed in neuromelanin-containing (dopaminergic) neurons. Lewy bodies in PD n igra neurons exhibited intense HO-1 immunostaining in their peripherie s. In both PD and control specimens, neuronal HO-1 staining was faint or nondetectable in the other brain regions surveyed. The fraction of GFAP-positive astroglia expressing HO-1 in PD substantia nigra (77.1 /- 12.3) was significantly greater than that observed in the substanti a nigra of control subjects (18.7 +/- 7.1; P = 0.0015). In the other r egions examined, percentages of GFAP-positive astroglia coexpressing H O-1 were relatively low and did not differ significantly (P > 0.05) be tween control and PD specimens. Upregulation of HO-1 in the substantia nigra of PD subjects supports the view that the affected tissue is ex periencing chronic oxidative stress. In addition, excessive cellular l evels of heme-derived free iron and carbon monoxide resulting from HO- 1 overactivity may contribute to the pathogenesis of PD. (C) 1998 Acad emic Press.