Glia maturation factor levels are elevated in the striatum and substantia nigra in Parkinson's disease

Abstract

Glia maturation factor (GMF) is an inflammatory protein, discovered in our laboratory, plays a major role in the pathogenesis of CNS inflammatory diseases. Although GMF has been implicated as a major contributing factor in the pathogenesis of EAE, an animal model of Multiple Sclerosis, there has not been a direct demonstration of GMF expression in human PD brains. In the present study we demonstrate a significant up regulation of GMF expression in human PD brain. Human brain tissues were obtained from autopsy, with PMI less than 6 h, at UI Deeded Body Program. For the comparison, we examined brain tissue from cases with clinically diagnosed and neuropathologically confirmed Parkinson's disease and age‐matched non‐PD controls. Our results show degenerating TH‐ immunostained neurons/ fibers associated with activated microglia and astrocytes in the autopsied brain from PD case. In PD brain, GMF appears to be localized to activated astrocytes and dopaminergic neurons. Additionally, we quantitatively estimated GMF protein by ELISA in different regions of PD brains. We demonstrated a significant increase (over 10 fold) in GMF levels in the substantia nigra and striatum of human PD brains compare to non‐PD. Thus, our results provide strong evidence that under conditions of neurodegeneration in PD the expression of GMF is significantly upregulated. (Supported by VA Merit Review award and NINDS grant NS073670).