Expression of ubiquitin-like immunoreactivity in axons after compression trauma to rat spinal cord

Abstract

The ubiquitin-mediated proteolytic pathway is an important mode of protein degradation in various tissues. Since breakdown of proteins may occur in axons after injury we evaluated the presence of ubiquitin-like immunoreactive material in rat spinal cord following compression injury of mild, moderate and severe degrees at T8-9 level, resulting in no neurological deficit, reversible paraparesis and paraplegia of the hind limbs, respectively. Rats with mild to severe compression injury surviving 1-4 days showed numerous, intensely immunoreactive expanded axons at the site of compression. The labelled axons were randomly distributed in the longitudinal tracts but they were never found in the corticospinal tracts. No labelling was detected by 9 days after injury. In addition, the presence of labelled axons was investigated in the T7 and the T10 segments from rats with moderate compression. No labelling was seen in T7, but in T10 segments many immunoreactive axons were present. Control rats did not show immunoreactive axons in the spinal cord. Neurons of dorsal root ganglia, trigeminal ganglia and of the grey matter of the spinal cord were immunoreactive. Cerebral cortical neurons did not show ubiquitin expression. Thus, compression of the rat spinal cord causes a transient accumulation of ubiquitin-like immunoreactive material in axonal swellings. Even though the dynamics of ubiquitin conjugates are not fully understood, the observed axonal accumulation presumably reflects arrested anterograde axonal transport of protein chiefly derived from neurons of dorsal root ganglia and the local neurons of the spinal cord. The presence of ubiquitin in damaged axons is one prerequisite for degradation of abnormal proteins by the ubiquitin-mediated proteolytic pathway, which may be activated in reactive axonal swellings.

Accumulation of immunoreactivity to ubiquitin carboxyl‐terminal hydrolase PGP 9.5 in axons of human cases with spinal cord lesions

“…Reactive axonal swelling is one characteristic property of many neuropathological processes, particularly after trauma to the brain or spinal cord (1, 8, 14, 15, 20-22). We and other groups have previously shown that such swellings contain immunoreactivity to ubiquitin (2,16,19,23). Our present demonstration of PGP 9.5 immunoreactivity in axonal swellings following lesions to the human spinal cord indicates that this enzyme is present in the swellings and can facilitate the utilization of ubiquitin in the degradation of proteins.…”

“…The temporal evolution of PGP 9.5 accumulation in axonal swellings of the human spinal cord cannot be assessed in our autopsy material. However, like ubiquitin, PGP 9.5 immunoreactivity quickly accumulates in axonal swellings following compression of rat spinal cord (16,17). Even after a mild compression trauma to rat spinal cord such immunoreactivity can be detected 4 h after injury (17).…”

A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration ( Wld S ) mouse

“…Ubiquitinated deposits accumulate in Alzheimer's disease neuritic plaques (20), Parkinson's disease Lewy bodies (21), and in the intranuclear inclusion bodies of polyglutamine diseases Huntington's chorea (22) and SCA1 (23). In the axon, ubiquitin accumulates in four-repeat tau transgenic mice (24) and following spinal cord injury (25). These reports suggest that the ubiquitin proteolytic pathway plays an important role in axonal degeneration as well as in neurodegeneration in general.…”

The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer’s Disease and Spinal Cord Injury

“…Compelling evidence indicates that the UPS also plays a role in the recovery from SCI (Coleman and Perry, 2002 ). While the accumulation/aggregation of ubiquitinated protein is a biomarker in the early response to SCI due to the impairment of proteasome function (Li and Farooque, 1996 ; Myeku et al, 2012 ), an increase in ubiquitin levels is essential for neuronal regeneration after SCI (Schwartz and Ciechanover, 2009 ; Noor et al, 2011 ). Furthermore, the UPS also has a role in neuronal development, differentiation, and programming of neuro-stem and neuroprogenitor cells.…”