Neuromelanin accumulation with age in catecholaminergic neurons from Macaca fascicularis brainstem

Neuromelanin (NM) is an auto-oxidation by-product of catecholamine synthesis which is observed almost exclusively in primates. We have estimated the distribution and the number of NM-positive neurons of the upper brainstem and the degree of their melanization from birth to the onset of senescence in 5 monkeys (Macaca fascicularis) aged 0, 1.5, 3.5, 8 and 13 years. Series of sections taken at 640-microns intervals were examined either unstained to detect unstained NM, stained for NM with Masson silver impregnation or processed by tyrosine hydroxylase (TH) immunohistochemistry to analyze catecholaminergic neurons. The proportion of NM-containing cells among TH-positive neurons varied from one catecholaminergic region to another: low in the hypothalamus and central gray substance (cgs); moderate in the cell group A8, and high in the ventral tegmental area (VTA), locus coeruleus (LC) and substantia nigra (SN). TH-positive neurons were detected in the SN, VTA, catecholaminergic cell group A8, LC, cgs and hypothalamus. At birth, although no unstained NM-positive neurons were detected, Masson-stained cells were observed, though only in the LC. At 1.5 and 3.5 years, Masson-positive neurons were observed despite the absence of visible pigment. At 8 and 13 years, unstained NM was present in Masson-positive neurons. The number of unstained NM-positive neurons and Masson-positive neurons and the amount of NM per neuron increased with age in each subregion studied. Nevertheless, some TH-positive neurons were found to be without NM. The data indicate a differential increased NM content with age in the neurons of midbrain catecholaminergic cell groups. However, its functional significance remains to be determined.