Nogo receptor deletion and multimodal exercise improve distinct aspects of recovery in cervical spinal cord injury.
We tested the ability of two plasticity-promoting approaches to enhance recovery in a mouse model of incomplete spinal cord injury (SCI). Genetically, we reduced myelin-mediated inhibition of neural plasticity through Nogo66-receptor (NgR) gene deletion. Behaviorally, we utilized a novel multimodal exercise training paradigm. Adult mice of wild-type or NgR-null genotype were subjected to partial lateral hemisection (LHx) at C3-C4 with the intent of producing anatomically and functionally mild deficits. Exercise training or control treatment proceeded for 14 weeks. Behavioral outcomes were assessed prior to tract tracing and histological analysis. Genotype and training exerted differing effects on performance; training improved performance on a test related to the training regimen (task-specific benefit), whereas genotype also improved performance on more generalized behaviors (task-non-specific benefit). There were no significant histological differences across genotype or training assignment with regard to lesion size or axonal tract staining. Thus either NgR gene deletion or exercise training benefits mice with mild cervical spinal injury. In this lesion model, the effects of NgR deletion and training were not synergistic for the tasks assessed. Further work is required to optimize the interaction between pharmacological and physical interventions for SCI.
Harel
Noam Y
NY
Department of Neurology, and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06520-8018, USA. noam.harel@yale.edu
Song
Kang-Ho
KH
Tang
Xin
X
Strittmatter
Stephen M
SM
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005081:Exercise Therapy; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000502:physiology; D017353:Gene Deletion; D005838:Genotype; D018737:Hand Strength / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000235:genetics* / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D000070816:Nogo Receptor 1; D010805:Physical Conditioning, Animal; D004856:Postural Balance / Q000502:physiology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology; D015203:Reproducibility of Results; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000534:rehabilitation* / Q000628:therapy*; D016138:Walking / Q000502:physiology
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C419790:Rtn4r protein, mouse; D012701:Serotonin
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