Factors regulating vagal sensory development: potential role in obesities of developmental origin.
Contributors to increased obesity in children may include perinatal under- or overnutrition. Humans and rodents raised under these conditions develop obesity, which like obesities of other etiologies has been associated with increased meal size. Since vagal sensory innervation of the gastrointestinal (GI) tract transmits satiation signals that regulate meal size, one mechanism through which abnormal perinatal nutrition could increase meal size is by altering vagal development, possibly by causing changes in the expression of factors that control it. Therefore, we have begun to characterize development of vagal innervation of the GI tract and the expression patterns and functions of the genes involved in this process. Important events in development of mouse vagal GI innervation occurred between midgestation and the second postnatal week, suggesting they could be vulnerable to effects of abnormal nutrition pre- or postnatally. One gene investigated was brain- derived neurotrophic factor (BDNF), which regulates survival of a subpopulation of vagal sensory neurons. BDNF was expressed in some developing stomach wall tissues innervated by vagal afferents. At birth, mice deficient in BDNF exhibited a 50% reduction of putative intraganglionic laminar ending mechanoreceptor precursors, and a 50% increase in axons that had exited fiber bundles. Additionally, BDNF was required for patterning of individual axons and fiber bundles in the antrum and differentiation of intramuscular array mechanoreceptors in the forestomach. It will be important to determine whether abnormal perinatal environments alter development of vagal sensory innervation of the GI tract, involving effects on expression of BDNF, or other factors regulating vagal development.
Fox
Edward A
EA
Behavioral Neurogenetics Laboratory, Ingestive Behavior Research Center, Department of Psychological Sciences, Purdue University, West Lafayette, IN 47907, USA. au_gc@psych.purdue.edu
Murphy
Michelle C
MC
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002232:Carbocyanines; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D009476:Neurons, Efferent / Q000502:physiology; D009765:Obesity / Q000503:physiopathology*; D011247:Pregnancy; D020813:Receptor, trkB / Q000502:physiology; D013270:Stomach / Q000196:embryology / Q000294:innervation; D014630:Vagus Nerve / Q000254:growth & development* / Q000502:physiology* / Q000503:physiopathology; D001616:beta-Galactosidase / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D002232:Carbocyanines; C072024:carbocyanine dye DiIC12(3); D020813:Receptor, trkB; D001616:beta-Galactosidase