Dataset Information

Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development.

ABSTRACT: S100B is expressed in various types of glial cells and is involved in regulating many aspects of their function. However, little is known about its role during nervous system development. In this study, we investigated the effect of inhibiting the onset of S100B synthesis in the development of the enteric nervous system, a network of neurons and glia located in the wall of the gut that is vital for control of gastrointestinal function. Intact gut explants were taken from embryonic day (E)13.5 mice, the day before the first immunohistochemical detection of S100B, and cultured in the presence of arundic acid, an inhibitor of S100B synthesis, for 48 h. The effects on Sox10-immunoreactive enteric neural crest progenitors and Hu-immunoreactive enteric neurons were then analyzed. Culture in arundic acid reduced the proportion of Sox10+ cells and decreased cell proliferation. There was no change in the density of Hu+ enteric neurons, however, a small population of cells exhibited atypical co-expression of both Sox10 and Hu, which was not observed in control cultures. Addition of exogenous S100B to the cultures did not change Sox10+ cell numbers. Overall, our data suggest that cell-intrinsic intracellular S100B is important for maintaining Sox10 and proliferation of the developing enteric glial lineage.

SUBMITTER: Hao MM

PROVIDER: S-EPMC5322270 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development.

Hao Marlene M MM Capoccia Elena E Cirillo Carla C Boesmans Werend W Vanden Berghe Pieter P

Frontiers in cellular neuroscience 20170223

S100B is expressed in various types of glial cells and is involved in regulating many aspects of their function. However, little is known about its role during nervous system development. In this study, we investigated the effect of inhibiting the onset of S100B synthesis in the development of the enteric nervous system, a network of neurons and glia located in the wall of the gut that is vital for control of gastrointestinal function. Intact gut explants were taken from embryonic day (E)13.5 mi ...[more]

PMID: 28280459

Similar Datasets

Project description:Impaired gut motility may contribute, at least in part, to the development of systemic hyperammonemia and systemic neurological disorders in inherited metabolic disorders, or in severe liver and renal disease. It is not known whether enteric neurotransmission regulates intestinal luminal and hence systemic ammonia levels by induced changes in motility. Here, we propose and test the hypothesis that ammonia acts through specific enteric circuits to influence gut motility. We tested our hypothesis by recording the effects of ammonia on neuromuscular transmission in tissue samples from mice, pigs, and humans and investigated specific mechanisms using novel mutant mice, selective drugs, cellular imaging, and enzyme-linked immunosorbent assays. Exogenous ammonia increased neurogenic contractions and decreased neurogenic relaxations in segments of mouse, pig, and human intestine. Enteric glial cells responded to ammonia with intracellular Ca2+ responses. Inhibition of glutamine synthetase and the deletion of glial connexin-43 channels in hGFAP::CreERT2+/-/connexin43f/f mice potentiated the effects of ammonia on neuromuscular transmission. The effects of ammonia on neuromuscular transmission were blocked by GABAA receptor antagonists, and ammonia drove substantive GABA release as did the selective pharmacological activation of enteric glia in GFAP::hM3Dq transgenic mice. We propose a novel mechanism whereby local ammonia is operational through GABAergic glial signaling to influence enteric neuromuscular circuits that regulate intestinal motility. Therapeutic manipulation of these mechanisms may benefit a number of neurological, hepatic, and renal disorders manifesting hyperammonemia.NEW & NOTEWORTHY We propose that local circuits in the enteric nervous system sense and regulate intestinal ammonia. We show that ammonia modifies enteric neuromuscular transmission to increase motility in human, pig, and mouse intestine model systems. The mechanisms underlying the effects of ammonia on enteric neurotransmission include GABAergic pathways that are regulated by enteric glial cells. Our new data suggest that myenteric glial cells sense local ammonia and directly modify neurotransmission by releasing GABA.

Dataset Information

Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development.

Publications

Arundic Acid Prevents Developmental Upregulation of S100B Expression and Inhibits Enteric Glial Development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets