DOI
https://doi.org/10.25772/C6FX-DY74
Defense Date
2015
Document Type
Thesis
Degree Name
Master of Science
Department
Physiology
First Advisor
Liya Qiao
Second Advisor
John R. Grider
Third Advisor
Janina P. Lewis
Abstract
Visceral hypersensitivity is the heightened response to sensory stimuli. Visceral sensations are transmitted through primary afferent neurons in the dorsal root ganglion (DRG) and the sensitization of the neural pathway leads to modification in spinal ascending and descending neurons. The aim of this investigation is to determine the effects of brain-derived neurotrophic factor (BDNF) and its signaling pathway on sensory neuronal activation during colitis. In order to evaluate this, levels of calcitonin-gene related peptide (CGRP), a neuropeptide marker for nociceptive transmission, and phosphorylated cAMP-response element binding protein (pCREB), a molecular switch in neuronal plasticity, were studied in response to BDNF in vivo and in vitro. Colitis caused an increase in the levels of CGRP and pCREB in thoracolumbar DRG, which was attenuated by BDNF neutralizing antibody and PLC inhibitor, U73122, but not PI3K inhibitor, LY294002. BDNF-induced CGRP expression and CREB activation in DRG culture was also blocked by PLC inhibitor, U73122, but not PI3K inhibitor, LY294002, or MEK kinase inhibitor, PD98059. These results suggest a unique signaling pathway, i.e. the PLC-γ pathway, is mediating BDNF action on sensory neuronal activation during colitis.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
7-23-2015