title: Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon.
abstract: Postnatal changes in the enteric nervous system (ENS) are involved in the establishment of colonic motility. In adult rats, butyrate induced neuroplastic changes in the ENS, leading to enhanced colonic motility. Whether butyrate can induce similar changes during the postnatal period remains unknown. Enemas (Na-butyrate) were performed daily in rat pups between postnatal day (PND) 7 and PND 17. Effects of butyrate were evaluated on morphological and histological parameters in the distal colon at PND 21. The neurochemical phenotype of colonic submucosal and myenteric neurons was analyzed using antibodies against Hu, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS). Colonic motility and neuromuscular transmission was assessed in vivo and ex vivo. Butyrate (2.5 mM) enemas had no impact on pup growth and histological parameters compared with control. Butyrate did not modify the number of Hu-immunoreactive (IR) neurons per ganglia. A significant increase in the proportion (per Hu-IR neurons) of nNOS-IR myenteric and submucosal neurons and ChAT-IR myenteric neurons was observed in the distal colon after butyrate enemas compared with control. In addition, butyrate induced a significant increase in both nitrergic and cholinergic components of the neuromuscular transmission compared with control. Finally, butyrate increased distal colonic transit time compared with control. We concluded that butyrate enemas induced neuroplastic changes in myenteric and submucosal neurons, leading to changes in gastrointestinal functions. Our results support exploration of butyrate as potential therapy for motility disorders in preterm infants with delayed maturation of the ENS.
authors.affiliation: INSERM, UMR913, Nantes, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Suply
authors.forename: Philine
authors.initials: P
authors.lastname: de Vries
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Soret
authors.forename: François
authors.initials: F
authors.lastname: Cossais
authors.forename: Michel
authors.initials: M
authors.lastname: Neunlist
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002087:Butyrates / Q000008:administration & dosage*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004733:Enema; D005769:Gastrointestinal Motility / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D002087:Butyrates; D052248:Nitric Oxide Synthase Type I; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine