Acute and prolonged hindlimb exercise elicits different gene expression in motoneurons than sensory neurons after spinal cord injury

Abstract

We examined gene expression in the lumbar spinal cord and the specific response of motoneurons, intermediate gray and proprioceptive sensory neurons after spinal cord injury and exercise of hindlimbs to identify potential molecular processes involved in activity dependent plasticity. Adult female rats received a low thoracic transection and passive cycling exercise for 1 or 4 weeks. Gene expression analysis focused on the neurotrophic factors; brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), and their receptors because of their potential roles in neural plasticity. We also examined expression of genes involved in the cellular response to injury; heat shock proteins (HSP) -27 and -70, glial fibrillary acidic protein (GFAP) and caspases -3, -7, and -9. In lumbar cord samples, injury increased the expression of mRNA for TrkB, all three caspases and the HSPs. Acute and prolonged exercise increased expression of mRNA for the neurotrophic factors BDNF and GDNF, but not their receptors. It also increased HSP expression and decreased caspase-7 expression, with changes in protein levels complimentary to these changes in mRNA expression. Motoneurons and intermediate grey displayed little change in mRNA expression following injury, but acute and prolonged exercise increased levels of mRNA for BDNF, GDNF and NT-4. In large DRG neurons, mRNA for neurotrophic factors and their receptors were largely unaffected by either injury or exercise. However, caspase mRNA expression was increased by injury and decreased by exercise. Our results demonstrate that exercise affects expression of genes involved in plasticity and apoptosis in a cell specific manner and that these change with increased post-injury intervals and/or prolonged periods of exercise.

Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury

“…Possible mechanisms of rehabilitation/training-mediated recoveries could be a combination of cellular, molecular, and trophic effects induced within the central nervous system (CNS) (Foret et al, 2010;Houle and Cote, 2013;Kao et al, 2009;Ying et al, 2005). Indeed, previous studies demonstrated exercise-dependent enhancement of neurotrophin production and secretion (Cote et al, 2011;Keeler et al, 2012), corticospinal tract growth and plasticity (Oh et al, 2009), and synaptic plasticity (Flynn et al, 2013). However, studies on the effect of exercise training on morphological, trophic, and synaptic changes in spared motoneurons that are anatomically intact below the level of injury have been emerging (Gazula et al, 2004).…”

Passive cycling in neurorehabilitation after spinal cord injury: A review

“…In adult rats that received a low thoracic spinal transection and PC exercise for 1 or 4 weeks, the gene expression in the lumbar spinal cord as well as the specific response of motoneurons, intermediate gray and proprioceptive sensory neurons was examined to identify potential molecular processes involved in activity dependent plasticity after SCI. 19 Following SCI, motoneurons and intermediate gray displayed small change in mRNA expression, but acute and prolonged exercise increased levels of mRNA for brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor and neurotrophin-4. In dorsal root ganglion neurons, mRNAs for neurotrophic factors and their receptors were largely unaffected by either injury or exercise, while caspase mRNA expression was increased by injury and decreased by exercise.…”

Gene expression analysis of neurotrophins, Trk receptors, and associated regulatory molecules after contusive spinal cord injury.

“…Similarly, in a recent study assessing mRNA and protein changes after transection at 10 and 31 days post injury, whole spinal cord TrkB mRNA was elevated at 10 days post injury, and whole spinal cord NT3 and TrkB protein was elevated at 31 days post injury, with expression differences also observed depending on the location within the parenchyma of the spinal cord (Keeler BE 2012). Table 1 summarizes the findings of recent experiments to facilitate comparison of these results.…”

“…However, these have largely focused on time points of less than 6 weeks Liebl, Huang et al 2001;Liebl DJ 2001;Widenfalk J 2001;Qiao and Vizzard 2002;Gulino R 2004;Zvarova, Murray et al 2004;Qiao and Vizzard 2005;Qiao LY 2005;Qian DX 2006;Li XL 2007;Hajebrahimi, Mowla et al 2008;Qian, Zhang et al 2011;Qian DX 2011;Keeler BE 2012). Although valuable for elucidating the role of neurotrophin signaling in the first 6 weeks after SCI, these data are of uncertain value for relating to longer-term post-SCI function.…”

“…Hence, it is important to examine not only the spinal cord, but also the sensory neurons that provide signals to the spinal cord, and to consider that the effects of SCI on the afferent neurons may differ in relation to the SCI, and/or to the tissues they innervate (Qiao and Vizzard 2002;Zvarova, Murray et al 2004;Bedi, Yang et al 2010;Bedi, Lago et al 2012;Keeler BE 2012). With these considerations in mind, it is important to consider that the spatial parameters of experiments, with regard to both the level of SCI and how the SCI affects the tissue investigated, can significantly influence the outcome.…”