Enteric GFAP expression and phosphorylation in Parkinson's disease

Authors

  • Thomas Clairembault,

    1. Inserm U913, Nantes, France
    2. University Nantes, Nantes, France
    3. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
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  • Willem Kamphuis,

    1. Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
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  • Laurène Leclair-Visonneau,

    1. Inserm U913, Nantes, France
    2. University Nantes, Nantes, France
    3. Inserm CIC-04, Nantes, France
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  • Malvyne Rolli-Derkinderen,

    1. Inserm U913, Nantes, France
    2. University Nantes, Nantes, France
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  • Emmanuel Coron,

    1. Inserm U913, Nantes, France
    2. University Nantes, Nantes, France
    3. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
    4. Inserm CIC-04, Nantes, France
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  • Michel Neunlist,

    1. Inserm U913, Nantes, France
    2. University Nantes, Nantes, France
    3. CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France
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  • Elly M. Hol,

    1. Astrocyte Biology & Neurodegeneration, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands
    2. Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam, the Netherlands
    3. Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands
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  • Pascal Derkinderen

    Corresponding author
    1. Inserm U913, Nantes, France
    2. University Nantes, Nantes, France
    3. Inserm CIC-04, Nantes, France
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  • Read the Editorial Highlight for this article on page 729.

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.

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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.

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