title: Slit2/Robo1 promotes synaptogenesis and functional recovery of spinal cord injury.
abstract: Neuronal network reconstruction is a pivotal determinant for functional recovery after spinal cord injury (SCI), the process of which includes synaptogenesis. Slit2 protein has been identified as a key regulator of axon regeneration and synapse formation in the vertebrate. Meanwhile, RhoA is the converging cascade of inhibitory molecules that interrupt synaptic plasticity in SCI. In the present study, we investigated the interaction among Slit2, Robo1, and RhoA and the potential roles of Slit2 in the pathological process of SCI. We showed that Slit2 was decreased, whereas Robo1 and RhoA were increased in the same surviving neurons in the spinal cord following SCI. We also found that inhibition of Slit2 led to upregulation of the expression of Robo1 and RhoA. However, the severe dysfunctions of the locomotor performance induced by SCI were reversed by treatments of Slit2-N, the active portion of Slit2, knockdown of Robo1 by the RNAi lentivirus, or inhibition of RhoA by the C3 exoenzyme, respectively. Further results suggested that downregulation of Slit2 and therefore upregulation of Robo1 and RhoA inhibited the activity of growth cone and hindered the formation of new synapses of surviving neurons near the injury sites of the spinal cord following SCI. Our study indicated a new mechanism of deficiency of synaptogenesis during the development of SCI and provided a potential strategy for the treatment of SCI.
authors.affiliation: Institute of Anesthesiology & pain (IAP), PET-CT and Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Hubei Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Xueqin
authors.initials: X
authors.lastname: Xu
authors.forename: Ruoshi
authors.initials: R
authors.lastname: Shi
authors.forename: Juying
authors.initials: J
authors.lastname: Liu
authors.forename: Wanjun
authors.initials: W
authors.lastname: Yao
authors.forename: Changbin
authors.initials: C
authors.lastname: Ke
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008124:Locomotion / Q000235:genetics; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000628:therapy*; D018709:Statistics, Nonparametric; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D014161:Transduction, Genetic; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D020742:rhoA GTP-Binding Protein; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein