Date of Award
Doctor of Philosophy (PhD)
Committee Member 1
Committee Member 2
Terry L. Powley
Committee Member 3
Vagal afferents transmit signals regarding food-derived stimuli in the gastrointestinal (GI) tract to the brain. Vagal mechanoreceptors called intraganglionic laminar endings (IGLEs) innervate the smooth muscle wall of GI organs and detect stretch and tension to regulate GI reflexes and satiation. Brain-derived neurotrophic factor (BDNF) is expressed in the smooth muscle of developing GI organs when vagal afferents from the nodose ganglion begin to innervate the GI tract. Therefore, it was hypothesized BDNF is necessary for development of vagal afferents that innervate this tissue. Targeted smooth muscle-specific BDNF homozygous knockout (BDNF SM -/-) mice were generated and .vagal afferent innervation and analysis of feeding behavior were compared to wild type (wt) mice. IGLEs and axons in the GI tract were labeled by injection of the nerve tracer horseradish peroxidase conjugated to wheatgerm agglutinin (WGA-HRP) into the nodose ganglion. Nodose ganglion neurons were also quantified to investigate the contribution of vagal sensory neurons to IGLE density. Meal pattern and microstructure analyses were used to determine if any underlying changes in the mechanisms that regulate feeding were associated with altered vagal function. Contrary to expectations for knockout (KO) of a growth factor gene, BDNF SM -/- mice showed increased IGLE density in the intestine compared to controls, whereas those supplying the stomach exhibited normal density. BDNF SM -/- mice showed an
increase in total vagal sensory neuron number compared to wild type (wt) mice as well as increases in the number of larger-diameter longitudinal axon bundles in the intestine. BDNF SM -/- mice exhibited decreases in meal duration and meal size compared to wt mice, suggesting food is more satiating in BDNF SM -/- mice compared to controls. Mutants also showed increased satiety ratio, suggesting a given amount of food produced greater satiety. Consistent with vagal afferent mediation of increased satiation in mutants, initial rate of food intake was similar in mutants and controls, but the subsequent sustained intake rate over min 6-30 was reduced in mutants. The increase in vagal sensory neuron and axon bundle numbers in BDNF SM -/- mice suggests GI BDNF may normally suppress survival of vagal GI afferents.
Biddinger, Jessica Erin, "Smooth Muscle-Specific Removal of Brain-Derived Neurotrophic Factor Results in Increased Vagal Afferent Innervation to the Intestine and Increased Satiation in Mice" (2013). Open Access Dissertations. 180.