title: Changes of synapses in experimental autoimmune encephalomyelitis by using Fasudil.
abstract: The ROCK signaling pathway is involved in numerous fundamental cellular functions such as cell migration, apoptosis, inflammatory responses, and neurite outgrowth. Previous studies demonstrate that Fasudil exhibited therapeutic potential of experimental autoimmune encephalomyelitis (EAE) possibly through immune-modulation and anti-inflammation. In this study, we observed the effect of Fasudil on synaptic protection of EAE mice. Fasudil ameliorated the clinical severity of EAE and inhibited Rho kinase (ROCK), especially ROCK II, in brain and spinal cord of EAE mice. Protein extracts from spinal cord of Fasudil-treated EAE mice promoted the formation of neurite outgrowth when co-cultured with primary neurons, indicating that peripheral administration of Fasudil can enter the central nervous system (CNS) and exhibited its biological effect on the formation of neurite outgrowth. Synapse-related molecule synaptophysin was enhanced, and CRMP-2, AMPA receptor, and GSK-3β were declined in spinal cord of Fasudil-treated mice. Neurotrophic factor BDNF and GDNF as well as immunomodulatory cytokine IL-10 in spinal cord were elevated in Fasudil-treated mice, while inflammatory cytokine IL-17, IL-1β, IL-6, and TNF-α were obviously inhibited, accompanied by the decrease of inflammatory M1 iNOS and the increase of anti-inflammatory M2 Arg-1, providing a microenvironment that contributes to synaptic protection. Our results indicate that Fasudil treatment protected against synaptic damage and promoted synaptic formation, which may be related with increased neurotrophic factors as well as decreased inflammatory microenvironment in the CNS of EAE mice.
authors.affiliation: Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China.
authors.forename: Jie-Zhong
authors.initials: JZ
authors.lastname: Yu
authors.affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Yong-Fei
authors.initials: YF
authors.lastname: Zhao
authors.affiliation: Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China.
authors.forename: Hai-Fei
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Meng
authors.affiliation: Institute of Brain Science, Department of Neurology, Medical School, Shanxi Datong University, Datong, China.|"2011" Collaborative Innovation Center/Research Center of Neurobiology, Shanxi University of Traditional Chinese Medicine, Taiyuan, China.
authors.forename: Cun-Gen
authors.initials: CG
authors.lastname: Ma
authors.affiliation: Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Xiao
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D038362:Glycogen Synthase Kinase 3; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects*
chemical_list: D016207:Cytokines; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D038362:Glycogen Synthase Kinase 3; C049347:fasudil