Date on Master's Thesis/Doctoral Dissertation
8-2013
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Anatomical Sciences and Neurobiology
Committee Chair
Petruska, Jeffrey Charles
Author's Keywords
Contusion; Neurotrophin; Trk receptor; mRNA expression; Spinal cord injury; Transcriptional analysis
Subject
Spinal cord--Wounds and injuries; Spinal nerves--Wounds and injuries; Nerves--Growth; Nervous system--Regeneration
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. Additionally, we sought to determine if the regulatory patterns we observed were perhaps due to an inflammatory molecule that mediated the coordinated expression pattern that we observed at 12 weeks post injury, and identified the chemokine CCL2 as a potential candidate gene.
Recommended Citation
Hougland, Matthew Tyler 1982-, "Gene expression analysis of neurotrophins, Trk receptors, and associated regulatory molecules after contusive spinal cord injury." (2013). Electronic Theses and Dissertations. Paper 640.
https://doi.org/10.18297/etd/640
