Abstract
Traumatic spinal cord injury (SCI) results in changes to the anatomical, neurochemical, and physiological properties of cells in the central and peripheral nervous system. Neurotrophins, acting by binding to their cognate Trk receptors on target cell membranes, contribute to modulation of anatomical, neurochemical, and physiological properties of neurons in sensorimotor circuits in both the intact and injured spinal cord. Neurotrophin signaling is associated with many post-SCI changes including maladaptive plasticity leading to pain and autonomic dysreflexia, but also therapeutic approaches such as training-induced locomotor improvement. Here we characterize expression of mRNA for neurotrophins and Trk receptors in lumbar dorsal root ganglia (DRG) and spinal cord after two different severities of mid-thoracic injury and at 6 and 12 weeks post-SCI. There was complex regulation that differed with tissue, injury severity, and survival time, including reversals of regulation between 6 and 12 weeks, and the data suggest that natural regulation of neurotrophins in the spinal cord may continue for months after birth. Our assessments determined that a coordination of gene expression emerged at the 12-week post-SCI time point and bioinformatic analyses address possible mechanisms. These data can inform studies meant to determine the role of the neurotrophin signaling system in post-SCI function and plasticity, and studies using this signaling system as a therapeutic approach.
Highlights
Traumatic injury to the spinal cord (SC) results in a variety of changes to sensorimotor circuits
The neurotrophins Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), and Neurotrophin 3 (NT3) are secreted growth factors that were first characterized for their important role in the survival of subpopulations of sensory neurons and in formation of SC sensorimotor circuits during development (e.g., Barbacid, 1995; Lindsay, 1996; Huang and Reichardt, 2001)
INJURY CHARACTERIZATION To assess the degree of injury severity, we characterized SC injuries based on two parameters; behavior as measured by BBB, and the amount of spared white matter (SWM) at the epicenter after staining with eriochrome cyanin (Rabchevsky et al, 2007)
Summary
Traumatic injury to the spinal cord (SC) results in a variety of changes to sensorimotor circuits. The neurotrophins Nerve Growth Factor (NGF), Brain Derived Neurotrophic Factor (BDNF), and Neurotrophin 3 (NT3) are secreted growth factors that were first characterized for their important role in the survival of subpopulations of sensory neurons and in formation of SC sensorimotor circuits during development (e.g., Barbacid, 1995; Lindsay, 1996; Huang and Reichardt, 2001). In addition to these essential roles in establishing the physiological patterns of developing neural circuitry, neurotrophins are implicated as having a role in activity-dependent changes associated with restoration of function after SCI (described below)
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