Cytochrome c oxidase defects of the human substantia nigra in normal aging

Based on morphological, biochemical, and molecular biologic analyses, degeneration of the dopaminergic nigrostriatal system has been reported to occur with normal aging. In the present study, the substantia nigra of 36 human brains with normal aging was investigated by means of morphometry and immunohistochemistry. The anteromedial (Am), anterointermediolateral (Ail), posteromedial (Pm), and posterolateral (Pl) nuclei of the substantia nigra were analyzed using antibodies directed against the subunits II/III of cytochrome c oxidase (COX), the complex IV of the respiratory chain. The numerical density of melanin-positive neurons with COX defects was significantly increased in the four investigated nuclei, namely Am, Ail, Pm, and Pl. These cells did not show any histologic signs of degeneration. The numerical density of melanin-positive neurons without COX defects was decreased with aging. The data of the present study indicate that complex IV defects of neurons in the substantia nigra might be one cause of neuronal dysfunction occurring during aging.