Increased expression of colony-stimulating factor-1 in mouse spinal cord with experimental autoimmune encephalomyelitis correlates with microglial activation and neuronal loss
Increased expression of colony-stimulating factor-1 in mouse spinal cord with experimental autoimmune encephalomyelitis correlates with microglial activation and neuronal loss
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DOI：
10.1002/glia.23464
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发表时间：
2018-10-01
期刊：
影响因子：
6.2
通讯作者：
Bo, Xuenong
中科院分区：
文献类型：
--
作者：
Gushchina, Svetlana;Pryce, Gareth;Bo, Xuenong
小胶质细胞有助于多发性硬化症各个阶段的病理生理学。集落刺激因子 1 (CSF1) 对于小胶质细胞增殖和激活至关重要。在这项研究中，我们测量了 CSF1 水平并研究了其在患有实验性自身免疫性脑脊髓炎 (EAE) 的小鼠脊髓中的细胞表达，以探索 CSF1 在神经元死亡中的潜在贡献。 ELISA 数据显示，急性和慢性 EAE 小鼠脊髓中的 CSF1 水平显着高于正常小鼠和注射佐剂的小鼠。免疫组织化学研究表明，CSF1 在正常小鼠脊髓的星形胶质细胞和神经元中表达。在急性 EAE 中，CSF1 表达显着增加，尤其是在外周白质和大运动神经元的星形胶质细胞中。在急性 EAE 中，运动神经元在灰质中观察到高密度的活化小胶质细胞，其中运动神经元表达高水平的 CSF1。在慢性 EAE 中观察到显着的大量运动神经元损失，并且具有高水平 CSF1 的剩余运动神经元被小胶质细胞包裹。病毒载体介导脊髓神经元中 CSF1 的过度表达，诱导注射部位小胶质细胞的深度增殖和激活，以及小胶质细胞包裹 CSF1 转导的神经元及其神经突。病毒注射后 2 周和 3 周观察到大的 CSF1 转导神经元显着损失。 CSF1 转导区域的脱髓鞘也很显着。这些结果表明，CNS 中的 CSF1 上调可能在 EAE 中小胶质细胞的增殖和激活中发挥重要作用，从而导致神经炎症和神经变性。 (c) 2018 年 Wiley 期刊公司。
Microglia contribute to pathophysiology at all stages of multiple sclerosis. Colony-stimulating factor-1 (CSF1) is crucial for microglial proliferation and activation. In this study we measured the CSF1 levels and studied its cellular expression in the mouse spinal cords with experimental autoimmune encephalomyelitis (EAE) to explore the potential contribution of CSF1 in neuronal death. ELISA data showed that CSF1 levels were significantly higher in the spinal cords with acute and chronic EAE than those of normal and adjuvant-injected mice. Immunohistochemical studies demonstrated that CSF1 was expressed in astrocytes and neurons in normal mouse spinal cord. In acute EAE, CSF1 expression was significantly increased, especially in astrocytes in peripheral white matter and large motoneurons. High density of activated microglia was observed in the gray matter where motoneurons expressed high-level CSF1 in acute EAE. Significant large motoneuron loss was seen in chronic EAE and the remaining motoneurons with high-level CSF1 were enwrapped by microglia. Viral vector mediated over-expression of CSF1 in spinal neurons induced profound proliferation and activation of microglia at the injection site and microglia enwrapped CSF1-transduced neurons and their neurites. Significant loss of large CSF1-transduced neurons was seen at 2 and 3 weeks post-viral injection. Demyelination in the CSF1-transduced areas was also significant. These results implicate that CSF1 upregulation in CNS may play an important role in the proliferation and activation of microglia in EAE, contributing to neuroinflammation and neurodegeneration. (c) 2018 Wiley Periodicals, Inc.