Enteric GFAP expression and phosphorylation in Parkinson's disease

Abstract

Enteric glial cells (EGCs) are in many respects similar to astrocytes of the central nervous system and express similar proteins including glial fibrillary acidic protein (GFAP). Changes in GFAP expression and/or phosphorylation have been reported during brain damage or central nervous system degeneration. As in Parkinson's disease (PD) the enteric neurons accumulate a-synuclein, and thus are showing PDspecific pathological features, we undertook the present survey to study whether the enteric glia in PD become reactive by assessing the expression and phosphorylation levels of GFAP in colonic biopsies. Twenty-four PD, six progressive supranuclear palsy (PSP), six multiple system atrophy (MSA) patients, and 21 age-matched healthy controls were included. The expression levels and the phosphorylation state of GFAP were analyzed in colonic biopsies by western blot. Additional experiments were performed using real-time PCR for a more precise analysis of the GFAP isoforms expressed by EGCs. We showed that GFAPj was the main isoform expressed in EGCs. As compared to control subjects, patients with PD, but not PSP and MSA, had significant higher GFAP expression levels in their colonic biopsies. The phosphorylation level of GFAP at serine 13 was significantly lower in PD patients compared to control subjects. By contrast, no change in GFAP phosphorylation was observed between PSP, MSA and controls. Our findings provide evidence that enteric glial reaction occurs in PD and further reinforce the role of the enteric nervous system in the initiation and/or the progression of the disease.

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice

“…In the present study, neuronal densities in the hippocampus were not reduced further in the TBI+ Cr group, indicating that the exacerbation of brain injury was confined to the cortical lesion. It should be noted that increased EGC reactivity and mucosal barrier dysfunction are also features of chronic neurodegenerative disorders, such as Parkinson’s disease 64 . In parallel, altered EGC reactivity was evident in TBI+ Cr colons in conjunction with increased paracellular permeability during active inflammation in the gut and chronic neuroinflammation in the brain.…”

Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker

“…Intriguingly, mouse enteric glial can undergo neurogenesis in response to injury [3]. In addition, enteric GFAP levels and phosphorylation are also increased in Parkinson's disease (PD) patients [11]. Further investigation is needed to understand the possible implications of this finding in PD patients.…”

Enteric Glial Cells: Recent Developments and Future Directions

“…Indeed, similarly to the brain, GFAP expression is increased in colonic biopsy specimens from patients with Parkinson disease as compared with patients with atypical parkinsonism or healthy controls. 67 The functional consequences of these changes on gut functions or their meaning as potential biomarkers of disease evolution remain to be determined.…”