Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) regulate development
of overlapping populations of vagal sensory neurons. During development, they are
expressed in GI smooth muscle, a tissue innervated by vagal mechanoreceptors. To investigate
the contributions of this BDNF and NT-3 to vagal development, they were ablated from
smooth muscle (smBDNF-KO, smNT-3-KO). As GI vagal afferents signal meal termination
(satiation), adult meal patterns were utilized as a functional assay of altered GI
vagal development. smNT-3-KO mice exhibited a decrease in meal-induced c-Fos activation
in the solitary tract nucleus and area postrema compared to controls, suggesting vagal
afferent innervation of the gut was decreased. Consistent with this, smNT-3-KO mice
showed increased meal duration, and increased size of their first daily meal, suggesting
vagal satiation signaling was reduced. In contrast, smBDNF-KO mice had increased intestinal
vagal mechanoreceptor innervation. Increased numbers of vagal sensory neurons and
intestinal fiber bundles in the knockout mice suggested this was due to increased
survival of intestinal vagal mechanoreceptors. Thus, BDNF may normally suppress survival
of these mechanoreceptors, counter to expectations for a growth factor. smBDNF-KO
mice ate meals of shorter duration and smaller size than controls, suggesting the
increased intestinal innervation provided increased satiation signaling. The opposite
effects of smBDNF-KO and smNT-3-KO on GI vagal sensory development/function may result
from interactions of smooth muscle-derived BDNF, but not NT-3, with the low affinity
nerve growth factor receptor, p75. This receptor is expressed by vagal afferent neurons
during development and its activation by BDNF typically results in cell death.
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© 2015 Published by Elsevier Inc.