Enteric GFAP expression and phosphorylation in Parkinson's disease
Enteric GFAP expression and phosphorylation in Parkinson's disease
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DOI：
10.1111/jnc.12742
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发表时间：
2014-09-01
影响因子：
4.7
通讯作者：
Derkinderen, Pascal
中科院分区：
文献类型：
--
作者：
Clairembault, Thomas;Kamphuis, Willem;Derkinderen, Pascal
肠胶质细胞（EGC）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，包括胶质纤维酸性蛋白（GFAP）。据报道，在脑损伤或中枢神经系统变性期间，GFAP 表达和/或磷酸化会发生变化。由于在帕金森病 (PD) 中，肠神经元积累 β-突触核蛋白，因此表现出 PD 特异性病理特征，我们进行了本次调查，通过评估结肠活检中 GFAP 的表达和磷酸化水平来研究 PD 中的肠神经胶质细胞是否变得反应性。包括 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。通过蛋白质印迹分析结肠活检中 GFAP 的表达水平和磷酸化状态。使用实时 PCR 进行了其他实验，以更精确地分析 EGC 表达的 GFAP 亚型。我们发现 GFAP 是 EGC 中表达的主要亚型。与对照受试者相比，PD 患者的结肠活检中 GFAP 表达水平显着升高，但 PSP 和 MSA 则没有。与对照受试者相比，PD 患者中 GFAP 丝氨酸 13 的磷酸化水平显着降低。相比之下，PSP、MSA 和对照之间没有观察到 GFAP 磷酸化的变化。我们的研究结果提供了证据表明肠神经胶质反应发生在帕金森病中，并进一步强化了肠神经系统在疾病发生和/或进展中的作用。
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 -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 GFAP 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.