Altered gastrointestinal motility involving autoantibodies in the experimental autoimmune encephalomyelitis model of multiple sclerosis.
Altered gastrointestinal motility involving autoantibodies in the experimental autoimmune encephalomyelitis model of multiple sclerosis.
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DOI：
10.1111/nmo.13349
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发表时间：
2018-09
影响因子：
3.5
通讯作者：
Mawe GM
中科院分区：
文献类型：
--
作者：
Spear ET;Holt EA;Joyce EJ;Haag MM;Mawe SM;Hennig GW;Lavoie B;Applebee AM;Teuscher C;Mawe GM
多发性硬化症（MS）是一种中枢神经系统的自身免疫性疾病，除了运动、感觉和认知症状外，还导致便秘，对此了解甚少。在这里，我们的特征胃肠道（GI）运动障碍的实验性自身免疫性脑脊髓炎（EAE）小鼠模型的MS和评估自身抗体是否靶向肠神经系统（ENS）和引起运动障碍。在雄性SJL和B6小鼠中诱导EAE。在野生型（WT）和B细胞缺陷小鼠中体内和离体评估GI运动性。MS和EAE血清用于调查ENS中的潜在靶点，并使用免疫组织化学表征ENS结构的变化。EAE小鼠出现胃排空加速和整个GI转运延迟，结肠运动减少。粪便含水量减少，结肠移行性肌电复合体（CMMC）和慢波频率降低。来自EAE小鼠的结肠表现出胶质细胞中GFAP水平降低。来自MS患者和来自EAE小鼠的血清靶向ENS神经元和神经胶质。EAE中B细胞缺乏可防止结肠动力障碍。与MS中经历的症状一致，我们证明EAE小鼠广泛表现出GI运动障碍的特征，在没有外在神经支配的情况下持续存在，表明ENS神经回路的直接参与。在患有EAE的B细胞缺陷型小鼠中不存在GI运动障碍，以及EAE和MS血清对ENS靶点的免疫反应性表明MS可以归类为已知诱导自身免疫性GI运动障碍的其他疾病。
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system that, in addition to motor, sensory, and cognitive symptoms, also causes constipation, which is poorly understood. Here, we characterize gastrointestinal (GI) dysmotility in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS and evaluate whether autoantibodies target the enteric nervous system (ENS) and cause dysmotility. EAE was induced in male SJL and B6 mice. GI motility was assessed in vivo and ex vivo in wild type (WT) and B cell-deficient mice. MS and EAE serum was used to survey potential targets in the ENS and changes in the ENS structure were characterized using immunohistochemistry. EAE mice developed accelerated gastric emptying and delayed whole GI transit with reduced colonic motility. Fecal water content was reduced, and colonic migrating myoelectrical complexes (CMMC) and slow waves were less frequent. Colons from EAE mice exhibited decreased GFAP levels in glia. Sera from MS patients and from EAE mice targeted ENS neurons and glia. B-cell deficiency in EAE protected against colonic dysmotility. Consistent with symptoms experienced in MS, we demonstrate that EAE mice widely exhibit features of GI dysmotility that persisted in the absence of extrinsic innervation, suggesting direct involvement of ENS neurocircuitry. The absence of GI dysmotility in B cell-deficient mice with EAE together with EAE and MS serum immunoreactivity against ENS targets suggests that MS could be classified among other diseases known to induce autoimmune GI dysmotility.
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影响因子：
6
作者：
CHIA, YW;FOWLER, CJ;SWASH, M
通讯作者：
SWASH, M
DOI：
10.1097/meg.0b013e328361eaf8
发表时间：
2013-09
影响因子：
2.1
作者：
Preziosi G;Raptis DA;Raeburn A;Thiruppathy K;Panicker J;Emmanuel A
通讯作者：
Emmanuel A
影响因子：
29.4
作者：
McClain J;Grubišić V;Fried D;Gomez-Suarez RA;Leinninger GM;Sévigny J;Parpura V;Gulbransen BD
通讯作者：
Gulbransen BD
影响因子：
24.5
作者：
Aubé, AC;Cabarrocas, J;Neunlist, M
通讯作者：
Neunlist, M
影响因子：
6
作者：
Hennessey, A;Robertson, NP;Compston, DAS
通讯作者：
Compston, DAS