Defense Date

2022

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Dr. Liya Qiao

Second Advisor

Dr. Gea-Ny Tseng

Third Advisor

Dr. Joseph Ritter

Abstract

Irritable Bowel Syndrome (IBS) is a functional gastrointestinal (GI) disorder marked by visceral hypersensitivity and changes in bowel function.Visceral sensation is initiated in the dorsal root ganglia (DRG) by primary afferent nerves that detect and transduce chemical and mechanical stimuli into electrical signals which relay to the central nervous system (CNS). The aim of this investigation was to characterize the role of Piezo2, a mechanically sensitive ion channel, located in nociceptive sensory afferents in the regulation of GI function in mice subjected to Water Avoidance Stress (WAS). Initially, body weight growth, colonic transit time, and somatic von Frey filament testing were used to characterize baseline changes in male and female mice after Piezo2 knockout from nociceptive afferent neurons (Piezo2cKO) and compared to Piezo2 intact (Piezo2wt) mice. Piezo2cKOhad a sex-dependent impact on GI function and mechanical sensitivity that impacted sensory homeostasis of female, but not male mice. Therefore, male mice were further tested for the role of Piezo2 in an animal model of WAS: WAS increased somatic mechanical sensitivity, slowed colonic transit time, and altered gait and stride patterns. Piezo2cKO attenuated WAS-induced somatic hypersensitivity and exacerbated WAS-induced reduction in colonic transit, but had no significant impact on WAS-induced sensory dysfunction assessed by gait assay. The expression of calcitonin gene-related peptide (CGRP) in DRG neurons was also increased by WAS in Piezo2wt mice, but not Piezo2cKO mice. These findings suggest Piezo2, in nociceptive neurons, plays a role in the modulation of visceral and somatic mechanosensitivity in a sex-dependent manner and participates in stress-induced GI dysfunction.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-12-2022

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