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Abstract
Spinal cord injury (SCI) leads to motor and sensory impairment below the site of injury, thereby necessitating rehabilitation. An enriched environment (EE) increases social interaction and locomotor activity in a mouse model, similar to human rehabilitation. However, the impact of EE on presynaptic plasticity in gene expression levels remains unclear. Hence, this study aimed to investigate the therapeutic potential of EE in an SCI mouse model. Mice with spinal cord contusion were divided into two groups: those housed in standard cages (control) and those in EE conditions (EE). Each group was housed separately for either 2- or 8-weeks post-injury, after which RNA sequencing was performed and compared to a sham group (receiving only a dorsal laminectomy). The synaptic vesicle cycle (SVC) pathway and related genes showed significant downregulation after SCI at both time points. Subsequently, we investigated whether exposure to EE for 2- and 8-weeks post-SCI could modulate the SVC pathway and its related genes. Notably, exposure to EE for 8 weeks resulted in a marked reversal effect of SVC-related gene expression, along with stimulation of axon regeneration and mitigation of locomotor activity loss. Thus, prolonged exposure to EE increased presynaptic activity, fostering axon regeneration and functional improvement by modulating the SVC in the SCI mouse model. These findings suggest that EE exposure proves effective in inducing activity-dependent plasticity, offering a promising therapeutic approach akin to rehabilitation training in patients with SCI.
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1 Inje University, Department of Rehabilitation Medicine, Ilsan Paik Hospital, Gyeonggi-do, South Korea (GRID:grid.411612.1) (ISNI:0000 0004 0470 5112); Yonsei University College of Medicine, Department of Medicine, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
2 Yonsei University College of Medicine, Department and Research Institute of Rehabilitation Medicine, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
3 Inje University, Department of Rehabilitation Medicine, Ilsan Paik Hospital, Gyeonggi-do, South Korea (GRID:grid.411612.1) (ISNI:0000 0004 0470 5112)
4 Yonsei University College of Medicine, Department of Pathology, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
5 Yonsei University College of Medicine, Department of Biomedical Sciences, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454); Yonsei University College of Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
6 Yonsei University Wonju College of Medicine, Department of Rehabilitation Medicine, Wonju, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
7 Yonsei University College of Medicine, Department and Research Institute of Rehabilitation Medicine, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454); Yonsei University College of Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
8 Yonsei University College of Medicine, Department and Research Institute of Rehabilitation Medicine, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454); Yonsei University College of Medicine, Graduate Program of Biomedical Engineering, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
9 Yonsei University College of Medicine, Department and Research Institute of Rehabilitation Medicine, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454); Yonsei University Wonju College of Medicine, Department of Rehabilitation Medicine, Wonju, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)
10 Yonsei University College of Medicine, Department and Research Institute of Rehabilitation Medicine, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454); Yonsei University College of Medicine, Graduate School of Medical Science, Brain Korea 21 Project, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454); Yonsei University College of Medicine, Graduate Program of Biomedical Engineering, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454); Yonsei University College of Medicine, Rehabilitation Institute of Neuromuscular Disease, Seoul, South Korea (GRID:grid.15444.30) (ISNI:0000 0004 0470 5454)