Role of Rho Kinase and Fasudil on Synaptic Plasticity in Multiple Sclerosis

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• 作者：Chan Chen ; Jie-Zhong Yu ; Qiong Zhang ; Yong-Fei Zhao…
• 关键词：Multiple sclerosis ; Synapse ; Cortical neuron ; Rho kinase ; Fasudil
• 刊名：NeuroMolecular Medicine
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：17
• 期：4
• 页码：454-465
• 全文大小：3,773 KB
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  Mueller, B. K., Mack, H., & Te
• 作者单位：Chan Chen (1) (3)
  Jie-Zhong Yu (2)
  Qiong Zhang (1)
  Yong-Fei Zhao (1)
  Chun-Yun Liu (2)
  Yan-Hua Li (2)
  Wan-Fang Yang (4)
  Cun-Gen Ma (2) (4)
  Bao-Guo Xiao (1)
  
  1. Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 12 Middle Wulumuqi Road, Shanghai, China
  3. Department of Rehabilitation, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai, China
  2. Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China
  4. -011-Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China
  
• 刊物主题：Neurosciences; Neurology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-1174

文摘

In addition to myelin loss and oligodendrocyte injury, axonal damage is a major cause of irreversible neurological disability in multiple sclerosis (MS). A series of studies have demonstrated that Rho kinase (ROCK) is involved in synaptic plasticity of neurons. Here, we found that ROCK activity in MS serum was elevated compared with serum from healthy controls. In experimental autoimmune encephalomyelitis (EAE), ROCK activity was also increased in serum, spleen, brain and spinal cord. Neuron injury with scratch and TNF-α stimulation induced the up-regulation of ROCK activity. When serum of MS patients was co-cultured with mouse cortical neurons in vitro, MS serum caused neurite shortening and reduction of cell viability, while the addition of Fasudil partially restored synaptic morphology of neurons, revealing that MS sera inhibited neurite outgrowth and synapse formation. The expression of synaptophysin was decreased in MS serum-neurons, and elevated in the presence of Fasudil. In contrast, the expression of phosphorylated collapsin response mediator protein-2 (CRMP-2) was elevated in MS serum-neurons and decreased in the presence of Fasudil. However, the addition of anti-ROCK I/II mixed antibodies in MS serum partially declined ROCK activity, but did not improve neurite outgrowth of neurons, revealing that Fasudil should prevent synaptic damage possibly through inhibiting intracellular ROCK activation mediated with MS serum. Our results indicate that axonal loss in MS may be related to increased ROCK activity. Fasudil could promote synaptogenesis and thus may contribute to preventing irreversible neurological disability associated with MS. Keywords Multiple sclerosis Synapse Cortical neuron Rho kinase Fasudil