title: Molecular and cellular changes in the lumbar spinal cord following thoracic injury: regulation by treadmill locomotor training.
abstract: Traumatic spinal cord injury (SCI) often leads to debilitating loss of locomotor function. Neuroplasticity of spinal circuitry underlies some functional recovery and therefore represents a therapeutic target to improve locomotor function following SCI. However, the cellular and molecular mechanisms mediating neuroplasticity below the lesion level are not fully understood. The present study performed a gene expression profiling in the rat lumbar spinal cord at 1 and 3 weeks after contusive SCI at T9. Another group of rats received treadmill locomotor training (TMT) until 3 weeks, and gene expression profiles were compared between animals with and without TMT. Microarray analysis showed that many inflammation-related genes were robustly upregulated in the lumbar spinal cord at both 1 and 3 weeks after thoracic injury. Notably, several components involved in an early complement activation pathway were concurrently upregulated. In line with the microarray finding, the number of microglia substantially increased not only in the white matter but also in the gray matter. C3 and complement receptor 3 were intensely expressed in the ventral horn after injury. Furthermore, synaptic puncta near ventral motor neurons were frequently colocalized with microglia after injury, implicating complement activation and microglial cells in synaptic remodeling in the lumbar locomotor circuitry after SCI. Interestingly, TMT did not influence the injury-induced upregulation of inflammation-related genes. Instead, TMT restored pre-injury expression patterns of several genes that were downregulated by injury. Notably, TMT increased the expression of genes involved in neuroplasticity (Arc, Nrcam) and angiogenesis (Adam8, Tie1), suggesting that TMT may improve locomotor function in part by promoting neurovascular remodeling in the lumbar motor circuitry.
authors: Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea ; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: Hae Young
authors: HY
authors: Shin
authors: Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea ; Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: Hyosil
authors: H
authors: Kim
authors: Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea ; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: Min Jung
authors: MJ
authors: Kwon
authors: Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea ; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: Dong Hoon
authors: DH
authors: Hwang
authors: Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea ; Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: KiYoung
authors: K
authors: Lee
authors: Department of Brain Science, Ajou University School of Medicine, Suwon, Republic of Korea ; Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Republic of Korea ; Department of Neurology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: Byung Gon
authors: BG
authors: Kim
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000473:pathology; D008159:Lumbar Vertebrae / Q000473:pathology* / Q000503:physiopathology; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010805:Physical Conditioning, Animal; D060066:Protein Interaction Maps / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics; D015203:Reproducibility of Results; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D013898:Thoracic Injuries / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics