Variable protein expression in the human substantia nigra

In Parkinson's disease (PD) there is a selective degeneration of dopamine neurons in the substantia nigra pars compacta (SNC), whilst neighbouring dopaminergic regions such as the ventral tegemental area (VT A) and retrorubral field are relatively preserved. Within the SNC, however variation in neuronal vulnerability is surprisingly large. Neurons in the ventral SNC exhibit early and marked neuronal death in PD, whilst those in the dorsal SNC subregions are relatively spared. Recent studies have suggested that a number of proteins are expressed exclusively in the more vulnerable neurons, however the variable vulnerability of dopaminergic neurons within the SNC brain region, have yet to be investigated in detail.The primary aim of this study was to investigate whether the vulnerable dopaminergic neurons in the ventral SNC exhibit any unique features that might explain their relative susceptibility in PD. Using immunohistochemistry to determine protein localisation at both the cellular and subregional level, in carefully defined anatomical regions, this study is the first to describe and compare the localisation, and relative amount, of proteins of interest in the different cell groups within the SNC in the healthy aged humans brain.No differences were identified in the localisation of the 12 proteins of interest explored in the midbrain dopamine subregions. However differences in the amount of two proteins, the trophic factor receptor Deleted in colorectal cancer and the active form of the dopamine uptake transporter, between the ventral and dorsal SNC were identified in the aged human brain. The data suggest that reduced levels of these proteins are likely to be involved in the vulnerability of the neurons in PD. These data increase our understanding regarding variable protein expression that may influence neuronal survival, and thus clinical symptoms, in PD. This knowledge may provide avenues for the development of novel strategies to improve the survival of neurons particularly susceptible to the disease process