TRIM32 affects the recovery of motor function following spinal cord injury through regulating proliferation of glia.

Qiang Fu,Yan Zhang,Jian-Wei Zhu,Mei Cheng,Wen-Jin Chen,Chun-Feng Liu,Quan-Hong Ma,Ru-Xiang Xu,Ming-Ming Zou

doi:10.18632/oncotarget.17492

Abstract

Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit the axonal regeneration after spinal cord injury (SCI). However, the underlying molecular mechanisms remain unclear. In the present study, we identify tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in glial cells in the normal uninjured spinal cord, exhibits strong expression in both astrocytes and microglia following SCI. We further observe that deficiency of TRIM32 results in increased numbers of astrocytes and microglia, which is accompanied by enhanced proliferation of both cells and increased secretion of interleukin (IL)-1 and IL-10. The axonal regeneration is impaired in the spinal cord of TRIM32−/− mice following SCI, which is indicated by increased distances of the corticospinal tracts (CST) fiber to the lesion site and less axonal sprouting. We further show that deficiency of TRIM32 results in delay motor recovery following SCI. Therefore, TRIM32 is a novel essential positive factor modulating axonal regeneration and the recovery of motor function following SCI, possibly through suppressing proliferation of glial cells.

Highlights

Spinal cord injury (SCI), lead to death of neurons, axonal damage and demyelination, eventually resulting in permanent motor, sensory and autonomic dysfunction, which is characterized by high morbidity and disability
We identify tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, which is barely detected in glial cells in the normal uninjured spinal cord, exhibits strong expression in both astrocytes and microglia following spinal cord injury (SCI)
Both the extrinsic environmental factors and intrinsic neuronal mechanisms limit the axonal regeneration after SCI

Summary

Introduction

Spinal cord injury (SCI), lead to death of neurons, axonal damage and demyelination, eventually resulting in permanent motor, sensory and autonomic dysfunction, which is characterized by high morbidity and disability. Hours to days later, nearby surviving tissue become vulnerable immediately, triggering a cascade of pathophysiological processes including biochemical vascular response and inflammation, which further promotes tissue degeneration leading to neurological dysfunction (referred to as secondary spinal cord injury) [2]. Reduction of these secondary pathophysiological events may contribute to functional recovery following SCI, and as one of potential prime strategies for repairing SCI. We present that deficiency of TRIM32 results in impairment in axonal regeneration and functional recovery after SCI through modulating proliferation of glial cells

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Results

Conclusion