Enteric Nervous System

Furness, John B.

doi:10.1007/978-3-540-29678-2_3035

Cited by 541 publications

(1,203 citation statements)

References 5 publications

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“…TSE neuroinvasion occurs in the periphery and results in dissemination to the brain via autonomic nerves, in particular parasympathetic and sympathetic efferent nerves projecting to the gut and thought to be common pathways (59). Developmental studies of the enteric nervous system (8,20,49) in young lambs are rare, but in one reported study (34) the number of neurons in the myenteric plexus of the rumen of suckling lambs was found to be 140 Ϯ 10 per cm 2 , whereas in young ruminating sheep (5 months of age) there were only 10 Ϯ 3 per cm 2 and in adult sheep, 7 Ϯ 2 per cm 2 . If this is reflected throughout the gut, the numbers of neurons for the uptake of PrP Sc /infectivity could be considerably reduced in weaned sheep compared with newborns.…”

Section: Survival Of Prpmentioning

confidence: 99%

Susceptibility of Young Sheep to Oral Infection with Bovine Spongiform Encephalopathy Decreases Significantly after Weaning

Hunter

Houston

Foster

et al. 2012

J Virol

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bBovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy (TSE) (or prion disease) that is readily transmissible to sheep by experimental infection and has the shortest incubation period in animals with the ARQ/ARQ PRNP genotype (at codons 136, 154, and 171). Because it is possible that sheep in the United Kingdom could have been infected with BSE by being fed contaminated meat and bone meal supplements at the same time as cattle, there is considerable interest in the responses of sheep to BSE inoculation. Epidemiological evidence suggests that very young individuals are more susceptible to TSE infection; however, this has never been properly tested in sheep. In the present study, low doses of BSE were fed to lambs of a range of ages (ϳ24 h, 2 to 3 weeks, 3 months, and 6 months) and adult sheep. The incidence of clinical BSE disease after inoculation was high in unweaned lambs (ϳ24 h and 2 to 3 weeks old) but much lower in older weaned animals The incubation period was also found to be influenced by the genotype at codon 141 of the PRNP gene, as lambs that were LF heterozygotes had a longer mean incubation period than those that were homozygotes of either type. The results suggest that sheep in the United Kingdom would have been at high risk of BSE infection only if neonatal animals had inadvertently ingested contaminated supplementary foodstuffs.T ransmissible spongiform encephalopathies (TSEs) are prion diseases that affect many mammals and are associated with the presence of the protein PrP Sc , a protease-resistant form of a normal host protein, PrP C . PrP Sc is believed to form all or part of the infectious agent (44). The natural sheep TSE is scrapie; however, sheep can also be experimentally infected with bovine spongiform encephalopathy (BSE) by several routes, including intracerebral, oral (17), and intravenous (28). The manifestation of clinical signs of BSE following inoculation depends upon a number of factors, the most important being the PRNP genotype. In the Neuropathogenesis Unit, Edinburgh, United Kingdom (NPU), Cheviot sheep, animals homozygous for the ARQ PRNP gene allele (codons 136, 154, and 171 indicated in order) are most susceptible (23). However, for reasons that are currently unknown, a various number of adult ARQ/ARQ sheep will survive a challenge with BSE (16). Understanding this aspect of resistance is of fundamental importance. One potential influence on disease outcome following infection with any TSE is the age at which the individual is challenged. Because of the etiology of scrapie, which suggests that in sheep the risk for infection is very high during the perinatal period, many sheep challenge studies, including the study described in reference 3, have used young lambs rather than adult sheep as infection models. In addition, epidemiological studies in cattle (15) have suggested that in general, younger individuals are more susceptible to infection with BSE, and studies in human beings have shown that more individuals at relatively young ages have b...

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Section: Survival Of Prpmentioning

confidence: 99%

Susceptibility of Young Sheep to Oral Infection with Bovine Spongiform Encephalopathy Decreases Significantly after Weaning

Hunter

Houston

Foster

et al. 2012

J Virol

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“…Together, our data uncover a previously unsuspected mechanism underlying development of centrifugal tubular organization and identify a previously unidentified effector of Shh in axon guidance. T he enteric nervous system is the largest peripheral nervous subsystem, often likened to a second brain (1). Embedded in the gastrointestinal tract, it controls various aspects of digestive function ranging from movement and secretion to absorption.…”

mentioning

confidence: 99%

“…Embedded in the gastrointestinal tract, it controls various aspects of digestive function ranging from movement and secretion to absorption. Despite their final location, enteric neurons are of neural crest origin, and the majority of enteric progenitors are derived from vagal neural crest cells at midgestation stages of the mouse embryo (1,2). Under the control of glial cell-derived neurotrophic factor (GDNF) and Endothelin 3 (END3) signaling, they migrate into the anterior gut mesenchyme.…”

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confidence: 99%

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Gas1 is a receptor for sonic hedgehog to repel enteric axons

Jin

Martinelli

Zheng

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The myenteric plexus of the enteric nervous system controls the movement of smooth muscles in the gastrointestinal system. They extend their axons between two peripheral smooth muscle layers to form a tubular meshwork arborizing the gut wall. How a tubular axonal meshwork becomes established without invading centrally toward the gut epithelium has not been addressed. We provide evidence here that sonic hedgehog (Shh) secreted from the gut epithelium prevents central projections of enteric axons, thereby forcing their peripheral tubular distribution. Exclusion of enteric central projections by Shh requires its binding partner growth arrest specific gene 1 (Gas1) and its signaling component smoothened (Smo) in enteric neurons. Using enteric neurons differentiated from neurospheres in vitro, we show that enteric axon growth is not inhibited by Shh. Rather, when Shh is presented as a point source, enteric axons turn away from it in a Gas1-dependent manner. Of the Gαi proteins that can couple with Smo, G protein α Z (Gnaz) is found in enteric axons. Knockdown and dominant negative inhibition of Gnaz dampen the axon-repulsive response to Shh, and Gnaz mutant intestines contain centrally projected enteric axons. Together, our data uncover a previously unsuspected mechanism underlying development of centrifugal tubular organization and identify a previously unidentified effector of Shh in axon guidance.enteric neuron | axon guidance | chemorepellent | Hedgehog | Gas1

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“…This is particularly so in the enteric nervous system, where careful immunohistochemical studies of the 'chemical coding' of different populations of enteric nerves showed that some neurons contain up to five neuropeptides. For example, Dogiel type 1 neurons contain bombesin, vasoactive intestinal polypeptide, cholecystokinin, galanin and enkephalin, as well as its primary transmitter ACh [35]. Some of the released peptides appear to play neuromodulatory roles, others long-term (trophic) roles, but for others their roles remain a mystery.…”

Section: Future Directionsmentioning

confidence: 99%

Purinergic Cotransmission

Burnstock

Verkhratsky

2012

Purinergic Signalling and the Nervous System

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ATP is a cotransmitter with classical transmitters in most nerves in the peripheral nervous system and central nervous system, although the proportions vary between species and tissues and in different developmental, physiological and pathophysiological conditions. ATP is released together with noradrenaline and neuropeptide Y from sympathetic nerves. It is released as a cotransmitter with acetylcholine from parasympathetic nerves supplying the bladder, developing skeletal neuromuscular junctions and some neurons in the brain. It is also released with nitric oxide and vasoactive intestinal polypeptide from non-adrenergic inhibitory enteric nerves, with glutamate from primary afferent sensory nerves and in the hypothalamus, and with dopamine and 5-hydroxytryptamine from some neurons in the central nervous system. Cotransmission offers subtle, local variations in neurotransmission and neuromodulation mechanisms.

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Enteric Nervous System

Cited by 541 publications

References 5 publications

Susceptibility of Young Sheep to Oral Infection with Bovine Spongiform Encephalopathy Decreases Significantly after Weaning

Susceptibility of Young Sheep to Oral Infection with Bovine Spongiform Encephalopathy Decreases Significantly after Weaning

Gas1 is a receptor for sonic hedgehog to repel enteric axons

Purinergic Cotransmission

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