Inserm U913, Nantes, France; University Nantes, Nantes, France; CHU Nantes, Institut des Maladies de l'Appareil Digestif, Nantes, France.
J Neurochem. 2014 Sep;130(6):805-15. doi: 10.1111/jnc.12742. Epub 2014 Jun 6.
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.
肠胶质细胞（EGCs）在许多方面与中枢神经系统的星形胶质细胞相似，并表达相似的蛋白质，包括神经胶质纤维酸性蛋白（GFAP）。在脑损伤或中枢神经系统变性期间，已经报道了 GFAP 表达和/或磷酸化的变化。由于在帕金森病（PD）中，肠神经元积累α-突触核蛋白，因此表现出 PD 特异性的病理特征，因此我们进行了本研究，以通过评估结肠活检中 GFAP 的表达和磷酸化水平来研究 PD 中的肠胶质细胞是否发生反应。纳入了 24 名 PD、6 名进行性核上性麻痹（PSP）、6 名多系统萎缩（MSA）患者和 21 名年龄匹配的健康对照者。通过 Western blot 分析结肠活检中 GFAP 的表达水平和磷酸化状态。还进行了额外的实验，使用实时 PCR 更精确地分析 EGCs 表达的 GFAP 同工型。我们表明 GFAPκ是 EGCs 中表达的主要同工型。与对照组相比，PD 患者而不是 PSP 和 MSA 患者的结肠活检中 GFAP 表达水平显著更高。与对照组相比，PD 患者 GFAP 在丝氨酸 13 处的磷酸化水平显着降低。相比之下，PSP、MSA 和对照组之间的 GFAP 磷酸化没有变化。我们的研究结果提供了证据表明肠胶质细胞反应发生在 PD 中，并进一步加强了肠神经系统在疾病的起始和/或进展中的作用。我们发现与健康受试者和非典型帕金森病（MSA、多系统萎缩和 PSP）患者相比，帕金森病患者的肠胶质细胞中 GFAP 过度表达和低磷酸化。我们的研究结果提供了证据表明肠胶质细胞反应发生在 PD 中，但不在 PSP 和 MSA 中，并且进一步加强了肠神经系统在 PD 病理生理学中的作用。
