Parkinson’s Disease Dementia Patients: Expression of Glia Maturation Factor in the Brain

Abstract

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease characterized by the presence of dopaminergic neuronal loss and motor disorders. PD dementia (PDD) is a cognitive disorder that affects many PD patients. We have previously demonstrated the proinflammatory role of the glia maturation factor (GMF) in neuroinflammation and neurodegeneration in AD, PD, traumatic brain injury (TBI), and experimental autoimmune encephalomyelitis (EAE) in human brains and animal models. The purpose of this study was to investigate the expression of the GMF in the human PDD brain. We analyzed the expression pattern of the GMF protein in conjunction with amyloid plaques (APs) and neurofibrillary tangles (NFTs) in the substantia nigra (SN) and striatum of PDD brains using immunostaining. We detected a large number of GMF-positive glial fibrillary acidic protein (GFAP) reactive astrocytes, especially abundant in areas with degenerating dopaminergic neurons within the SN and striatum in PDD. Additionally, we observed excess levels of GMF in glial cells in the vicinity of APs, and NFTs in the SN and striatum of PDD and non-PDD patients. We found that the majority of GMF-positive immunoreactive glial cells were co-localized with GFAP-reactive astrocytes. Our findings suggest that the GMF may be involved in the pathogenesis of PDD.

Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies

“…Astrocytes showed an overexpression of CD44 and abnormal disease-related proliferation [62]. The overexpression of the glia maturation factor [GMF], a pro-inflammatory protein that has been demonstrated to orchestrate the immune cell-neuron-glia crosstalk in vitro and in animal models of PD [63], was also observed in the substantia nigra and corpus striatum of human PD brains, in close contact with areas of neuronal degeneration [64].…”