In this study, a comparative analysis of
metal-related neuronal vulnerability was performed in two brainstem nuclei, the locus coeruleus (LC) and substantia nigra (SN), known targets of the etiological
noxae in
Parkinson's disease and related disorders. LC and SN pars compacta neurons both degenerate in
Parkinson's disease and other Parkinsonisms; however, LC neurons are comparatively less affected and with a variable degree of involvement. In this study,
iron,
copper, and their major molecular forms like
ferritins,
ceruloplasmin,
neuromelanin (NM),
manganese-superoxide dismutase (SOD), and
copper/
zinc-SOD were measured in LC and SN of normal subjects at different ages.
Iron content in LC was much lower than that in SN, and the ratio
heavy-chain ferritin/
iron in LC was higher than in the SN. The NM concentration was similar in LC and SN, but the
iron content in NM of LC was much lower than SN. In both regions, heavy- and light-chain
ferritins were present only in glia and were not detectable in neurons. These data suggest that in LC neurons, the
iron mobilization and toxicity is lower than that in SN and is efficiently buffered by NM. The bigger damage occurring in SN could be related to the higher content of
iron.
Ferritins accomplish the same function of buffering
iron in glial cells.
Ceruloplasmin levels were similar in LC and SN, but
copper was higher in LC. However, the
copper content in NM of LC was higher than that of SN, indicating a higher
copper mobilization in LC neurons.
Manganese-SOD and
copper/
zinc-SOD had similar age trend in LC and SN. These results may explain at least one of the reasons underlying lower vulnerability of LC compared to SN in
Parkinsonian syndromes.