Investigation of non-traditional roles of the neural gut-brain axis

Davis, Elizabeth A.

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https://hdl.handle.net/2142/102415 Copy

Description

Title

Investigation of non-traditional roles of the neural gut-brain axis

Author(s)

Davis, Elizabeth A.

Issue Date

2018-11-02

Director of Research (if dissertation) or Advisor (if thesis)

Dailey, Megan J.

Doctoral Committee Chair(s)

Dailey, Megan J.

Committee Member(s)

• Christian, Catherine A.
• Raetzman, Lori T.
• Llano, Daniel A.

Department of Study

Neuroscience Program

Discipline

Neuroscience

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

gut-brain axis, autonomic, intestinal epithelium, stem cells

Abstract

The neural gut-brain axis is an important bidirectional pathway through which the gastrointestinal (GI) tract communicates with the central nervous system (CNS). This axis includes sensory nerves that send information from the GI tract to the brain and motor nerves that transmit descending information from the brain to the GI tract. Traditional research has focused on nutrient-induced changes in sensory neural signaling and the subsequent motor response altering muscular and secretory functions. These nerves, though, may also play novel, non-traditional roles in the function of the gut-brain axis. Just as nutrients have been shown to induce neuroplasticity of CNS neurons, long-term alterations in nutrition may do more than just change signaling, and ultimately lead to modifications in fiber density, branching, and terminal morphology. These neuroplastic changes may underlie aberrant signaling and could be associated with GI diseases, as has been found with CNS-associated neuroplasticity and disease. The GI tract also has to perform many functions beyond muscular contraction/relaxation and secretion. One essential function in maintaining GI homeostasis is the constant renewal of the cells lost due to normal apoptosis, a process whereby entire GI tissues can be replaced every few days. Because loss of the motor nerves of the gut-brain axis results in changes in the rate of tissue renewal and the location of the nerves are in close contact with the GI stem cells responsible for cell renewal, these motor nerves may play a direct role in inducing proliferation and differentiation of the GI tissue. I hypothesized that there are indeed new, non-traditional roles of the sensory and motor nerves of the gut-brain axis in neuroplasticity and tissue regeneration and tested the mechanisms underlying these processes. Specifically, I used rodents and swine mammalian models to develop new methods by which to investigate multiple hypotheses about nutrient-induced vagal sensory neuroplasticity and found a direct mechanism by which the autonomic motor nerves induce changes in intestinal epithelial renewal. The results of the experiments included in this dissertation establish roles for the neural gut-brain axis that are outside those that are traditionally studied, which can expand the available methods to manipulate gut-brain system for therapeutic purposes.

Graduation Semester

2018-12

Type of Resource

text

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http://hdl.handle.net/2142/102415

Copyright and License Information

Copyright 2018 Elizabeth Davis

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