Unexpected expression of alpha- and beta-globin in mesencephalic dopaminergic neurons and glial cells

The mesencephalic dopaminergic (mDA) cell system is composed by two major groups of projecting cells in the Substantia Nigra (A9 neurons) and the Ventral Tegmental Area (A10 cells). A9 neurons form the nigrostriatal pathway and are involved in regulating voluntary movements and postural reflexes. Their selective degeneration leads to Parkinson’s disease (PD). We used cDNA microarrays and nanoCAGE technology coupled with Laser Capture Microdissection (LCM) to characterize the intrinsic physiological properties of A9 DA neurons. Surprisingly, we found that these cells express alpha- and beta- chains of haemoglobin. Here we report that globin-immunoreactivity decorates the majority of A9 DA neurons, a subpopulation of cortical and hippocampal astrocytes as well as mature oligodendrocytes. This pattern of expression was confirmed in different mouse strains, in rat and human. This is the first report showing that haemoglobin is expressed in the Substantia Nigra of human post mortem brain. Our data suggest that the most famed oxygen-carrying globin is not exclusively restricted to the blood, but it may play a role in the normal physiology of the brain as well as in neurodegenerative disorders. To investigate the biological effects of globin expression, alpha- and beta- chains of mouse hemoglobin were overexpressed in MN9D dopaminergic neuroblastoma cell lines. RNA from 4 replicates each of over-expressing cells and of control samples, for a total of 8 samples, were hybridized on Affymetrix GeneChip Mouse Genome 430A 2.0 Arrays. Hybridization of one of the control samples did not pass quality assessment and the sample was therefore excluded from further analysis.