The role of brain -derived neurotrophic factor in the development of vagal innervation of the gastrointestinal tract
Abstract
Vagal sensory neurons are dependent on neurotrophins to survive programmed cell death during development. Neurotrophins, including BDNF, are expressed in developing stomach wall tissues innervated by vagal afferents. However, it is not known which neurotrophins contribute to the survival of gastrointestinal afferents. For this dissertation, I investigated the importance of BDNF for survival of this vagal innervation in the stomach, and based on its roles in other sensory systems, examined its effects on axon guidance and mechanoreceptor growth and differentiation. I employed postmortem anterograde tracing with DiI to label vagal projections to the stomach of early postnatal day (P)0, 3, 4, and 6 in wild-type mice (+/+) and mice lacking one (+/-) or both (-/-) copies of the BDNF gene. The stomach wall was scanned through all tissue layers with a confocal microscope at 80 equidistant sites, covering its entire ventral surface. Vagal axon bundles, individual vagal axons, and mechanoreceptors (intraganglionic laminar endings, IGLEs; intramuscular arrays, IMAs) were quantified at each of the 80 sites. Additionally, efferent terminals were quantified to determine whether effects associated with BDNF were sensory specific. Myenteric neurons, stained with Cuprolinic Blue, were also identified and quantified in order to determine whether losses in vagal innervation observed were associated with losses of their target cells, myenteric neurons. Putative IGLE precursor numbers were reduced by about 50% in homozygous mutants relative to wild types, whereas axon bundle numbers, individual axon densities, putative IMA precursor densities and efferent terminal numbers were similar in wild types and mutants. Additionally, in BDNF -/- mutants putative IMA precursors often exhibited truncated telodendria, and axon and fiber bundle patterning in the antrum was disorganized. These results provide the first evidence of BDNF roles in development of vagal gastric innervation, including survival (IGLEs), axon guidance (patterning of antral axons) and receptor growth/differentiation (IMAs).
Degree
Ph.D.
Advisors
Fox, Purdue University.
Subject Area
Neurosciences|Psychobiology|Physiological psychology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.