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Publication : Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation.

First Author  Fox EA Year  2013
Journal  Am J Physiol Regul Integr Comp Physiol Volume  305
Issue  11 Pages  R1307-22
PubMed ID  24068045 Mgi Jnum  J:201812
Mgi Id  MGI:5515825 Doi  10.1152/ajpregu.00337.2013
Citation  Fox EA, et al. (2013) Loss of neurotrophin-3 from smooth muscle disrupts vagal gastrointestinal afferent signaling and satiation. Am J Physiol Regul Integr Comp Physiol 305(11):R1307-22
abstractText  A large proportion of vagal afferents are dependent on neurotrophin-3 (NT-3) for survival. NT-3 is expressed in developing gastrointestinal (GI) smooth muscle, a tissue densely innervated by vagal mechanoreceptors, and thus could regulate their survival. We genetically ablated NT-3 from developing GI smooth muscle and examined the pattern of loss of NT-3 expression in the GI tract and whether this loss altered vagal afferent signaling or feeding behavior. Meal-induced c-Fos activation was reduced in the solitary tract nucleus and area postrema in mice with a smooth muscle-specific NT-3 knockout (SM-NT-3(KO)) compared with controls, suggesting a decrease in vagal afferent signaling. Daily food intake and body weight of SM-NT-3(KO) mice and controls were similar. Meal pattern analysis revealed that mutants, however, had increases in average and total daily meal duration compared with controls. Mutants maintained normal meal size by decreasing eating rate compared with controls. Although microstructural analysis did not reveal a decrease in the rate of decay of eating in SM-NT-3(KO) mice, they ate continuously during the 30-min meal, whereas controls terminated feeding after 22 min. This led to a 74% increase in first daily meal size of SM-NT-3(KO) mice compared with controls. The increases in meal duration and first meal size of SM-NT-3(KO) mice are consistent with reduced satiation signaling by vagal afferents. This is the first demonstration of a role for GI NT-3 in short-term controls of feeding, most likely involving effects on development of vagal GI afferents that regulate satiation.
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