Immunological detection of 4-hydroxynonenal protein adducts in developing pontine and Purkinje neurons and in karyorrhexis in pontosubicular neuronal necrosis.

Abstract Four-hydroxynonenal (HNE) has been proposed as an important marker of radical-induced lipid peroxidation. The principal objective of this study was to assess the occurrence of lipid peroxidation in normal perinatal brain and brains with one form of pontosubicular neuronal necrosis (PSN). Immunochemical studies using an antibody against HNE-modified protein were performed in controls aged from 20 weeks of gestation to 64 years, and patients with PSN. Immunohistochemical study showed developmental and aging changes of positive staining in Purkinje cells and pontine neurons (27 weeks–7 months, 50 and 64 years). In addition, karyorrhectic cells in pontine nuclei with PSN were positively stained. Immunoblotting revealed that a 75-kDa protein, which is speculated to be mitochondrial complex-1 protein, was the most intensely expressed among multiple immunoreactive proteins. Our results identified the presence of oxidative stress in the perinatal neuron, and this oxidative stress may contribute to some forms of karyorrhectic death.