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Different luminal nutrients activate distinct patterns of myenteric neurons

Tijdschriftbijdrage - Tijdschriftabstract Conferentiebijdrage

Background: Monitoring of ingested nutrients by an organism is essen-tial for balancing energy input. The gastrointestinal tract plays an im-portant role in this homeostasis. Nutrient signals sensed by specialized enteroendocrine cells in the epithelium are conveyed to the enteric nerv-ous system (ENS) to initiate intestinal reflexes facilitating digestion and absorption. However, the extent to which the ENS is ‘aware’ of the lumi-nal composition remains elusive. We addressed whether there are spe-cific enteric pathways dedicated to detecting different luminal nutrients.Methods: Calcium imaging was performed on intact jejunal prepara-tions from Wnt1- cre; R26R- GCaMP3 mice, which express the fluores-cent calcium indicator GCaMP3 in their ENS. Glucose (300 mM), acetate (100 mM), and L- phenylalanine (100 mM), as a model sugar, short chain fatty acid, and amino acid respectively, were perfused onto the mucosa whilst imaging the underlying enteric neurons. Nutrient transport or diffusion across the mucosa was mimicked by pressure ejecting nutri-ents from a micropipette impaled through the epithelium of a villus to target the containing nerve endings, or by applying nutrients onto gan-glia in peeled preparations. Responders were further classified by their cell size and neurochemistry using post-hoc immunolabeling.Results: Glucose, acetate, and L- phenylalanine perfused onto the mucosa each evoked Ca2+ transients in distinct subsets of my-enteric (17 ± 6%, 12 ± 2%, and 9 ± 2%) and submucosal neurons (21 ± 4%; 24 ± 7%, and 23 ± 3% of total neurons within the field of view, respectively). The cell size (P < 0.0001; One- way ANOVA) and proportions of calbindin+ and nNOS+ myenteric neurons that re-sponded differed significantly between the nutrients (P < 0.0001; χ2 test), while submucosal responders were predominantly cholinergic (98 ± 2% of total responders) and of similar size. Nutrients applied into villi or onto ganglia did not elicit neuronal responses, indicating that nutrients are first sensed at the epithelium.Conclusions: Different nutrients applied to the epithelium triggered distinct patterns of myenteric neuronal activation, suggesting that the ENS is able to discriminate between different compositions of luminal content such that it can act accordingly
Tijdschrift: Neurogastroenterology and Motility
ISSN: 1350-1925
Issue: S1
Volume: 32
Aantal pagina's: 1
Jaar van publicatie:2020