Don't die like me: Which proteins are responsible for the selective neuronal vulnerability within the substantia nigra?

A hallmark of Parkinson's disease is the specific degeneration of dopaminergic neurons in the substantia nigra pars compacta. Interestingly, not all of these neurons are affected to the same extent. Studies revealed that neurons located more ventrally within the substantia nigra pars compacta have a higher prevalence to degenerate than those located in the dorsal tier. The underlying reasons for this selective neuronal vulnerability are still unknown. The aim of the present study was to gain a better understanding of molecular differences between these two neuronal subpopulations that may explain the selective neuronal vulnerability within the human substantia nigra. For this purpose, the neurons from the ventral as well as dorsal tier of the substantia nigra were specifically isolated out of neuropathologically unremarkable human substantia nigra sections with laser microdissection. Following, their proteome was analyzed by data independent acquisition mass spectrometry. The samples were analysed donor-specifically and not pooled for this purpose. A total of 5,391 proteins were identified in the substantia nigra. Of these, 2,453 proteins could be quantified in 100% of the dorsal tier samples. 1,629 could be quantified in 100% of the ventral tier samples. Nine proteins were differentially regulated with a log2 value ≥0.5 and a Qvalue ≤0.05. Of these 7 were higher abundant in the dorsal tier and 2 higher in the ventral tier. These proteins are associated with the cytoskeleton, neuronal plasticity, or calcium homeostasis. With these findings a deeper understanding can be gained of the selective neuronal vulnerability within the substantia nigra and of protective mechanisms against neurodegeneration in specific neuronal subpopulations.

Is brain banking of psychiatric cases valuable for neurobiological research?: [review]

It is widely accepted that neurobiological abnormalities underlie the symptoms of psychiatric disorders such as schizophrenia and unipolar or bipolar affective disorders. New molecular methods, computer-assisted quantification techniques and neurobiological investigation methods that can be applied to the human brain are all used in post-mortem investigations of psychiatric disorders. The following article describes modern quantitative methods and recent post-mortem findings in schizophrenia and affective disorders. Using our brain bank as an example, necessary considerations of modern brain banking are addressed such as ethical considerations, clinical work-up, preparation techniques and the organization of a brain bank, the value of modern brain banking for investigations of psychiatric disorders is summarized.