B' Department of Neurology, Laboratory of Experimental Neurology and Neuroimmunology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.
Neurology Clinics and Neuroscience Laboratory, the Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
Glia. 2015 Oct;63(10):1772-83. doi: 10.1002/glia.22843. Epub 2015 Apr 27.
Exogenous transplanted neural precursor cells (NPCs) exhibit miscellaneous immune-modulatory effects in models of autoimmune demyelination. However, the regional interactions of NPCs with the host brain tissue in remissive inflammatory events have not been adequately studied. In this study we used the chronic MOG-induced Experimental Autoimmune Encephalomyelitis (EAE) model in C57BL/six mice. Based on previous data, we focused on neuropathology at Day 50 post-induction (D50) and studied the expression of connexin43 (Cx43) and Cx47, two of the main glial gap junction (GJ) proteins, in relation to the intraventricular transplantation of GFP(+) NPCs and their integration with the host tissue. By D50, NPCs had migrated intraparenchymally and were found in the corpus callosum at the level of the lateral ventricles and hippocampus. The majority of GFP(+) cells differentiated with simple or ramified processes expressing mainly markers of mature GLIA (GFAP and NogoA) and significantly less of precursor glial cells. GFP(+) NPCs expressed connexins and formed GJs around the hippocampus more than lateral ventricles. The presence of NPCs did not alter the increase in Cx43 GJ plaques at D50 EAE, but prevented the reduction of oligodendrocytic Cx47, increased the number of oligodendrocytes, local Cx47 levels and Cx47 GJ plaques per cell. These findings suggest that transplanted NPCs may have multiple effects in demyelinating pathology, including differentiation and direct integration into the panglial syncytium, as well as amelioration of oligodendrocyte GJ loss, increasing the supply of potent myelinating cells to the demyelinated tissue.
外源性移植的神经前体细胞 (NPCs) 在自身免疫性脱髓鞘模型中表现出多种免疫调节作用。然而，NPCs 与缓解性炎症事件中宿主脑组织的区域相互作用尚未得到充分研究。在本研究中，我们使用慢性 MOG 诱导的实验性自身免疫性脑脊髓炎 (EAE) 模型在 C57BL/six 小鼠中进行。基于先前的数据，我们专注于诱导后第 50 天 (D50) 的神经病理学，并研究了连接蛋白 43 (Cx43) 和 Cx47 的表达，这两种主要的神经胶质缝隙连接 (GJ) 蛋白之一，与 GFP(+) NPC 的脑室移植及其与宿主组织的整合有关。到 D50 时，NPC 已经向脑实质内迁移，并在侧脑室和海马体水平的胼胝体中发现。大多数 GFP(+) 细胞分化为具有简单或分支过程的细胞，表达主要成熟 GLIA（GFAP 和 NogoA）的标志物，而前体细胞的表达较少。GFP(+) NPC 表达连接蛋白，并在海马体周围形成 GJ 比侧脑室周围更多。NPC 的存在并没有改变 D50 EAE 时 Cx43 GJ 斑块的增加，但防止了少突胶质细胞 Cx47 的减少，增加了少突胶质细胞的数量、局部 Cx47 水平和每个细胞的 Cx47 GJ 斑块。这些发现表明，移植的 NPCs 可能在脱髓鞘病理中具有多种作用，包括分化和直接整合到神经胶质合胞体中，以及改善少突胶质细胞 GJ 丢失，增加有髓鞘形成细胞向脱髓鞘组织的供应。
