Neuronal changes in the substantia nigra with aging: a Golgi study.

In order to recognize substantia nigra neuronal changes occurring in aging, 20 human control brains from 13 males and 7 females with a mean age of 61 years (range 20 to 93 years) without neurological disease were examined using the Golgi method. A quantitative study of dendrites and dendritic spines was performed as well as a statistical analysis of obtained data. Parallel sections to the impregnated material were histologically and immunohistologically studied with the aim to identify possible neuronal cytoskeletal abnormalities. Results were compared to changes of substantia nigra reported in other conditions such as Parkinson's disease (PD) and methyl-4-phenylpyridine (MPTP) experimental toxicity. Three different substantia nigra neuronal types were observed. Morphological changes during aging consisted of distorted profile of the cell body and swelling and beading of dendritic branches. The quantitative assessment of changes observed in neuronal types showed a significant loss of dendrites and dendritic spines, especially in the oldest cases. These findings were similar to those previously described in other cerebral areas during aging, but a specific vulnerability of the largest substantia nigra neuronal type could be observed. Nodulations and beaded aspects of dendrites are reminiscent of those changes previously described in MPTP toxicity. Dendritic varicosities found in the oldest cases have also been found in dendrites of large substantia nigra neurons in PD. Cytoskeletal abnormalities have been described in PD but were not found in the present study. Therefore, other pathophysiological mechanisms different from the cytoskeletal compromise occurring in some neurodegenerative diseases should be involved in aging.