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

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.

SUBMITTER: Fu Q

PROVIDER: S-EPMC5542194 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Fu Qiang Q Zou Ming-Ming MM Zhu Jian-Wei JW Zhang Yan Y Chen Wen-Jin WJ Cheng Mei M Liu Chun-Feng CF Ma Quan-Hong QH Xu Ru-Xiang RX

Oncotarget 20170701 28

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 i ...[more]

PMID: 28514764

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Project description:The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4-5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.

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

Publications

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

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