Profile of immediate early gene expression in the lumbar spinal cord of low-thoracic paraplegic mice.

Abstract

Induction of immediate early gene (IEG) expression is believed to constitute one of the earliest steps in plasticity and long-term modification of neuronal properties. Although behavioral evidence of neuronal plasticity at the sublesional level after spinal cord injury exists, spatiotemporal changes of IEGs in spinal segments located caudally to such an injury have never been examined. Here, the authors studied spatiotemporal changes of c-fos, nor-1, nur77, nurr1, and retinoid x receptor (rxr) messenger RNA expression in the lumbar segments L1-L2 after low-thoracic spinal transection (Tx). C-fos expression generally increased in the dorsal horn with significant levels reached at 3 days and 14 days post-Tx. Basal nor-1 transcript levels decreased in the intermediate zone and dorsal horn areas at 7 days. Nur77 levels were nonsignificantly depressed throughout that period of time, whereas nurr1 and rxr transcripts were not detected before or after Tx. In conclusion, the results provide evidence of distinct roles for c-fos and nor-1 in reorganization and plasticity of neuronal networks typically involved in sensorimotor integration and locomotor control.

Plasticity in Sublesionally Located Neurons Following Spinal Cord Injury

“…Because peak levels were observed at 7 and 14 days post-Tx, the authors have proposed a role for these neurotrophic factors in spontaneous locomotor function recovery in untrained and otherwise nonstimulated complete paraplegic animals. Their finding nicely supports those reported previously with immediate early genes in complete paraplegic mice (Landry et al 2006b). In contrast, surprisingly, BDNF, NT-3, and synapsin-1 were found to display lower levels of expression in the lumbar cord of low-thoracic hemitransected and deafferentated rats (Gomez-Pinilla et al 2004).…”

“…For instance, recent experiments have shown that the expression of some immediate early genes (IEGs) is up-or downregulated in sublesional spinal cord areas within a few hours to a few days post-trauma. Landry and colleagues reported in low-thoracic spinal cord transected mice that c-fos and nor-1 were respectively increased and decreased in L1-L2 dorsal horn and intermediate zone areas (Landry et al 2006b). Increased fos-immunoreactive levels were also found as soon as at 2.5 h post-trauma in sublesional segments (low-thoracic and lumbar laminae I-IV, VII, VIII, and X) of high-thoracic or cervical spinal cord transected rats (Ruggiero et al 1997).…”

Synergistic Effects of D1/5 and 5-HT1A/7 Receptor Agonists on Locomotor Movement Induction in Complete Spinal Cord–Transected Mice

“…Another key factor that can affect CPG activation post spinal cord injury (SCI) is time. It is increasingly recognized that sublesional plasticity events that may affect CPG reorganization and excitability occur spontaneously within a few weeks to a few months post-SCI (e.g., see DISCUSSION in Landry et al 2006b). For instance, it was shown without intervention (i.e., no grafts, drugs, training, or tail stimulation) that low but significant levels of hindlimb movements may spontaneously occur in mice within a few weeks post-Tx in open-field or treadmill conditions (Guertin 2005;Lapointe et al 2006;Ung et al 2007).…”

Spontaneous recovery of hindlimb movement in completely spinal cord transected mice: a comparison of assessment methods and conditions

“…22,23 Although it would be beyond the scope of this paper to discuss the cellular mechanisms underlying such spontaneous recovery in Tx animals, recent results suggest a role for specific immediate early genes such as c-fos, Nor-1 and Nur77 as early genetic events that may lead to locomotor network reorganization and spontaneous activation. 24 Other transmembranal changes such as increased expression of subsets of serotonin, noradrenaline, glutamate and glycine receptors have also been proposed as factors that may contribute to functional recovery in Tx animals. [25][26][27] Why would performances 'level off' after 2-3 weeks with most assessment methods?…”