title: 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 α-synuclein, and thus are showing PD-specific 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 GFAPκ 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. We showed that GFAP is over-expressed and hypophosphorylated in the enteric glial cells (EGCs) of Parkinson's disease (PD) patients as compared to healthy subjects and patients with atypical parkinsonism (MSA, multiple system atrophy and PSP, progressive supranuclear palsy). Our findings provide evidence that enteric glial reaction occurs in PD but not in PSP and MSA and further reinforce the role of the enteric nervous system in the pathophysiology of PD.
authors.affiliation: Inserm U913, Nantes, France; University Nantes, Nantes, France; CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Clairembault
authors.forename: Willem
authors.initials: W
authors.lastname: Kamphuis
authors.forename: Laurène
authors.initials: L
authors.lastname: Leclair-Visonneau
authors.forename: Malvyne
authors.initials: M
authors.lastname: Rolli-Derkinderen
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Coron
authors.forename: Michel
authors.initials: M
authors.lastname: Neunlist
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
authors.forename: Pascal
authors.initials: P
authors.lastname: Derkinderen
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D002460:Cell Line; D003106:Colon / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D012694:Serine / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D012694:Serine
keywords: Parkinson's disease; enteric glial cells; enteric nervous system; glial fibrillary acidic protein; multiple system atrophy; progressive supranuclear palsy