Stavropoulos Filippos, Georgiou Elena, Sargiannidou Irene, Kleopa Kleopas A
Neuroscience Department, The Cyprus Institute of Neurology and Genetics, Nicosia 2371, Cyprus.
Center for Multiple Sclerosis and Related Disorders, The Cyprus Institute of Neurology and Genetics and Cyprus School of Molecular Medicine, Nicosia 2371, Cyprus.
Pharmaceuticals (Basel). 2021 Jun 28;14(7):621. doi: 10.3390/ph14070621.
Induction of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), in connexin 32 (Cx32) or Cx47 knockout (KO) mice with deficiency in oligodendrocyte gap junctions (GJs) results in a more severe disease course. In particular, Cx47 KO EAE mice experience an earlier EAE onset and more pronounced disease severity, accompanied by dysregulated pro-inflammatory responses preceding the disease manifestations. In this study, analysis of relevant pro-inflammatory cytokines in wild type EAE, Cx32 KO EAE, and Cx47 KO EAE mice revealed altered expression of preceding EAE [7 days post injection (dpi)], of at the onset of EAE (12 dpi), and of at the peak of EAE (24 dpi) in Cx47 KO EAE mice. Moreover, Cx47 KO EAE mice exhibited more severe blood-spinal cord barrier (BSCB) disruption, enhanced astrogliosis with defects in tight junction formation at the glia limitans, and increased T-cell infiltration prior to disease onset. Thus, Cx47 deficiency appears to cause dysregulation of the inflammatory profile and BSCB integrity, promoting early astrocyte responses in Cx47 KO EAE mice that lead to a more severe EAE outcome. Further investigation into the role of oligodendrocytic Cx47 in EAE and multiple sclerosis pathology is warranted.
在少突胶质细胞间隙连接（GJ）存在缺陷的连接蛋白32（Cx32）或Cx47基因敲除（KO）小鼠中诱导实验性自身免疫性脑脊髓炎（EAE），这是一种多发性硬化症（MS）的动物模型，会导致更严重的病程。特别是，Cx47基因敲除的EAE小鼠发病更早，疾病严重程度更明显，在疾病表现出现之前伴有促炎反应失调。在本研究中，对野生型EAE、Cx32基因敲除的EAE和Cx47基因敲除的EAE小鼠中相关促炎细胞因子的分析显示，Cx47基因敲除的EAE小鼠在EAE前期（注射后7天）、EAE发病时（12天）和EAE高峰期（24天）的相关因子表达发生了改变。此外，Cx47基因敲除的EAE小鼠表现出更严重的血脊髓屏障（BSCB）破坏、神经胶质增生增强，胶质界膜紧密连接形成存在缺陷，并且在疾病发作前T细胞浸润增加。因此，Cx47缺陷似乎会导致炎症特征和BSCB完整性失调，促进Cx47基因敲除的EAE小鼠早期星形胶质细胞反应，从而导致更严重的EAE结果。有必要进一步研究少突胶质细胞Cx47在EAE和多发性硬化症病理学中的作用。
