The brain to gut pathway: a possible route of prion transmission

Lawson, Victoria; Furness, John B.; Klemm, Helen M; Pontell, Louise; Chan, Ewan; Hill, Andrew F.; Chiocchetti, Roberto

doi:10.1136/gut.2010.222620

Cited by 31 publications

(28 citation statements)

References 56 publications

(58 reference statements)

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“…The enteric nervous system (ENS) exerts local control over mixing and propulsive movements in the intestine and this may also affect the L-cell renewal rate. In this view, prion infection of the ENS resembles typical pathologic changes observed in Parkinson's disease patients [42].…”

Section: Discussionmentioning

confidence: 66%

Foodborne Transmission of Bovine Spongiform Encephalopathy to Non-Human Primates Results in Preclinical Rapid-Onset Obesity

et al. 2014

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Obesity has become one of the largest public health challenges worldwide. Recently, certain bacterial and viral pathogens have been implicated in the pathogenesis of obesity. In the present study, we retrospectively analyzed clinical data, plasma samples and post-mortem tissue specimens derived from a risk assessment study in bovine spongiform encephalopathy (BSE)-infected female cynomolgus monkeys (Macaca fascicularis). The original study design aimed to determine minimal infectious doses after oral or intracerebral (i.c.) infection of macaques to assess the risk for humans. High-dose exposures resulted in 100% attack rates and a median incubation time of 4.7 years as described previously. Retrospective analyses of clinical data from high-dosed macaques revealed that foodborne BSE transmission caused rapid weight gain within 1.5 years post infection (β = 0.915; P<0.0001) which was not seen in age- and sex-matched control animals or i.c. infected animals. The rapid-onset obesity was not associated with impaired pancreatic islet function or glucose metabolism. In the early preclinical phase of oral transmission associated with body weight gain, prion accumulation was confined to the gastrointestinal tract. Intriguingly, immunohistochemical findings suggest that foodborne BSE transmission has a pathophysiological impact on gut endocrine cells which may explain rapid weight gain. To our knowledge, this is the first experimental model which clearly demonstrates that foodborne pathogens can induce obesity.

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Section: Discussionmentioning

confidence: 66%

Foodborne Transmission of Bovine Spongiform Encephalopathy to Non-Human Primates Results in Preclinical Rapid-Onset Obesity

et al. 2014

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“…Lawson and colleagues demonstrated that intracerebral inoculation with infectious prion protein resulted in the presence of infectious prions in the ileum at the time of clinical disease, about 220 days after inoculation (71). All animals displayed some degree of myenteric neuropathy, with loss of neurofilament M-expressing neurons in the myenteric plexus, though there were no major changes in the submucosal plexus.…”

Section: Role Of Enteric Glia In Brain Disordersmentioning

confidence: 99%

“…The first reveals enteric glia as targets for the misfolded (infective) isoform of the prion protein, which is responsible for transmissible spongiform encephalopathies such as variant Creutzfeldt-Jakob disease. Enteric glia express the normal cellular form the of the prion protein and have been implicated as a reservoir of infective prions, as they serve as a template for replication of the misfolded prion protein (70)(71)(72). Following intravenous, intraperitoneal, or intracerebral inoculation with infective prions, misfolded prion is found in enteric glia.…”

Section: Role Of Enteric Glia In Brain Disordersmentioning

confidence: 99%

Emerging roles for enteric glia in gastrointestinal disorders

Sharkey¹

2015

J. Clin. Invest.

159

131

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“…Evidence exists that prions can move in the opposite direction, from brain to gut (Kitamoto et al, 1989;Safar et al, 2008;Lawson et al, 2010), which may provide a clue to one way that sporadic prion disease becomes endemic in grazing animals ( Figure 2). In recent experiments, infective prion protein, PrP''^, was injected into the brains of healthy mice (Lawson et al, 2010).…”

Section: A Theory Of Prion Disease Transmission Between Grazing Animalsmentioning

confidence: 95%

“…In recent experiments, infective prion protein, PrP''^, was injected into the brains of healthy mice (Lawson et al, 2010). Tissue samples were taken when the mice had succumbed to chnical disease (6 to 8 mo).…”

Section: A Theory Of Prion Disease Transmission Between Grazing Animalsmentioning

confidence: 99%

NONRUMINANT NUTRITION SYMPOSIUM: Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract1,2

Furness

Poole

2012

Journal of Animal Science

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The functioning of the gastrointestinal tract is under the control of the most extensive system of peripheral neurons in the body, the enteric nervous system, and the largest endocrine system of the body, the GEP endocrine system. The enteric nervous system in large mammals contains 500 million neurons, and the GEP endocrine system produces more than 30 hormones. Numerous enteric neuropathies affecting both humans and animals have been described and digestive disorders affect commercially important species, such as horses and cattle. The most severe enteric neuropathies (e.g., lethal white syndrome in horses or Hirschsprung's disease in humans) can be fatal. Also, horses with ileus or other digestive disorders are commonly euthanized. In this review we discuss examples of enteric neuropathies that affect agricultural animals and humans: prion disease, postoperative ileus, distal enteric aganglionosis, and infective diarrhea. Enteric neurons and glia are a location of prion proteins and are involved in transmission of the infection from gut to brain and brain to gut. Postoperative ileus is a complex disorder involving the local inhibitory effects of sympathetic nervous system activation and the release of opioids, presumably from enteric neurons. Intestinal inflammation, especially of the external muscle that includes enteric ganglia, also occurs in ileus. Congenital distal bowel aganglionosis, responsible for lethal white syndrome in horses, Hirschsprung's disease in humans, and similar conditions in mice and rats, is a fatal condition if untreated. Mutations of the same genes can cause the condition in each of these species. The only effective current treatment is surgical removal of the aganglionic bowel. Infectious diarrheas involve activation of enteric secretomotor neurons by pathogens and the toxins they produce, which causes substantial fluid loss. Strategies to target enteric neurons in the treatment of secretory diarrheas have not been developed. Disorders of enteroendocrine cells, other than GEP endocrine tumors, are less well documented. However, evidence for the involvement of gut endocrine cells in a subset of patients with irritable bowel syndrome, and in the symptomology of celiac disease, has been demonstrated. Further investigation of the involvement of enteric neural and endocrine signaling systems in digestive disorders, especially in agricultural and companion animals, may lead to diagnostic and therapeutic advances.

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The brain to gut pathway: a possible route of prion transmission

Cited by 31 publications

References 56 publications

Foodborne Transmission of Bovine Spongiform Encephalopathy to Non-Human Primates Results in Preclinical Rapid-Onset Obesity

Foodborne Transmission of Bovine Spongiform Encephalopathy to Non-Human Primates Results in Preclinical Rapid-Onset Obesity

Emerging roles for enteric glia in gastrointestinal disorders

NONRUMINANT NUTRITION SYMPOSIUM: Involvement of gut neural and endocrine systems in pathological disorders of the digestive tract1,2

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