Altered production of nerve growth factor in aganglionic intestines

Kuroda, Takeshi; Ueda, Mitsuharu; Nakano, Miwako; Saeki, M

doi:10.1016/0022-3468(94)90334-4

Cited by 23 publications

(8 citation statements)

References 13 publications

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“…Chronic administration of nerve growth factor to newborn Wistar‐Kyoto rats leads to hypertrophy and hyperplasia of cardiac sympathetic neurons and cardiac catecholamine content that exceeds levels found in spontaneously hypertensive rats . Hypertrophy of the bladder or colon, as in Hirschsprung's disease, is also associated with elevated nerve growth factor levels, hypertrophy of autonomic neurons innervating the bladder or colon, and increased catecholamine synthesis and release . If nerve growth factor levels are similarly elevated in hypertrophied human hearts, then neurons in cardiac ganglia may hypertrophy as well.…”

Section: Introductionmentioning

confidence: 99%

Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

Singh

Sayers

Walter

et al. 2013

JAHA

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BackgroundAutonomic imbalances including parasympathetic withdrawal and sympathetic overactivity are cardinal features of heart failure regardless of etiology; however, mechanisms underlying these imbalances remain unknown. Animal model studies of heart and visceral organ hypertrophy predict that nerve growth factor levels should be elevated in heart failure; whether this is so in human heart failure, though, remains unclear. We tested the hypotheses that neurons in cardiac ganglia are hypertrophied in human, canine, and rat heart failure and that nerve growth factor, which we hypothesize is elevated in the failing heart, contributes to this neuronal hypertrophy.Methods and ResultsSomal morphology of neurons from human (579.54±14.34 versus 327.45±9.17 μm2; P<0.01) and canine hearts (767.80±18.37 versus 650.23±9.84 μm2; P<0.01) failing secondary to ischemia and neurons from spontaneously hypertensive rat hearts (327.98±3.15 versus 271.29±2.79 μm2; P<0.01) failing secondary to hypertension reveal significant hypertrophy of neurons in cardiac ganglia compared with controls. Western blot analysis shows that nerve growth factor levels in the explanted, failing human heart are 250% greater than levels in healthy donor hearts. Neurons from cardiac ganglia cultured with nerve growth factor are significantly larger and have greater dendritic arborization than neurons in control cultures.ConclusionsHypertrophied neurons are significantly less excitable than smaller ones; thus, hypertrophy of vagal postganglionic neurons in cardiac ganglia would help to explain the parasympathetic withdrawal that accompanies heart failure. Furthermore, our observations suggest that nerve growth factor, which is elevated in the failing human heart, causes hypertrophy of neurons in cardiac ganglia.

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Section: Introductionmentioning

confidence: 99%

Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

Singh

Sayers

Walter

et al. 2013

JAHA

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“…The residual weak SOX10 expression detected clearly came from extrinsic nerves originated from sources other than the vagal neural crest; the weak signals could probably also come from the glial cell population of the abnormal ganglia. We argue that in HD patients, SOX10 expressed in the affected sacral region may have abnormal interactions with neurotrophic factors38 43 44 or with acetylcholine receptor which could be transactivated by SOX10 ,45 and as a result stimulate the growth of cholinergic and other excitatory nerve fibres in the aganglionic bowel.…”

Section: Discussionmentioning

confidence: 93%

SOX10is abnormally expressed in aganglionic bowel of Hirschsprung's disease infants

Sham

Lui

et al. 2001

Gut

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Background-The primary pathology of Hirschsprung's disease (HD) is a congenital absence of ganglion cells in the caudal most gut. The spastic aganglionic bowel is often innervated by a network of hypertrophied nerve fibres. Recently, mutations of SOX10 have been identified in patients with HD but only in those with Waardenburg-Shah syndrome. Aims-To understand the molecular basis for the pathogenesis of HD we intended to determine the specific cell lineages in the enteric nervous system which normally express SOX10 but are aVected in disease conditions. Methods-We studied colon biopsies from 10 non-syndromic HD patients, aged three months to four years, and 10 age matched patients without HD as normal controls. The absence of mutation in the SOX10 gene of HD patients was confirmed by DNA sequencing. Expression and cellular distribution of SOX10 in bowel segments of normal and HD infants were examined by reverse transcriptionpolymerase chain reaction and in situ hybridisation. Results-We found that in normal infants and normoganglionic bowel segments of HD patients, SOX10 was expressed in both neurones and glia of the enteric plexuses and in the nerves among the musculature in normal colon. In the aganglionic bowel segments of patients, SOX10 expression was consistently lower and was found to be associated with the hypertrophic nerve trunks in the muscle and extrinsic nerves in the serosa. Conclusion-We conclude that SOX10 is normally required postnatally in the functional maintenance of the entire enteric nervous system, including neurones and glia. In non-syndromic HD patients who do not have the SOX10 mutation, the SOX10 gene expressed in the sacral region may be involved in the pathogenesis of the abnormal nerve trunks through interaction with other factors. (Gut 2001;49:220-226)

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“…Our in vitro study provides further evidence that expression of NGF in colon SMC is inducible by mechanical stretch. Up-regulation of NGF expression in distended bowel may also occur in chronic functional obstruction [20, 24]. Kuroda et al [20] observed that NGF mRNA expression in colon smooth muscle was increased in the dilated colon proximal to the aganglioned distal bowel in patients with Hirschsprung’s disease as well as in piebald lethal mouse [20].…”

Section: Discussionmentioning

confidence: 99%

“…Up-regulation of NGF expression in distended bowel may also occur in chronic functional obstruction [20, 24]. Kuroda et al [20] observed that NGF mRNA expression in colon smooth muscle was increased in the dilated colon proximal to the aganglioned distal bowel in patients with Hirschsprung’s disease as well as in piebald lethal mouse [20]. Interestingly, they found that the expression of NGF mRNA in the aganglioned distal bowel was not increased compared with normal subjects.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of abdominal pain in bowel obstruction: role of mechanical stress-induced upregulation of nerve growth factor in gut smooth muscle cells

Lin¹,

Winston³

et al. 2017

Pain

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Abdominal pain is one of the major symptoms in bowel obstruction (BO); its cellular mechanisms remain incompletely understood. We tested the hypothesis that mechanical stress in obstruction upregulates expression of nociception mediator nerve growth factor (NGF) in gut smooth muscle cells (SMC), and NGF sensitizes primary sensory nerve to contribute to pain in BO. Partial colon obstruction was induced with a silicon band implanted in the distal bowel of Sprague-Dawley rats. Colon-projecting sensory neurons in the dorsal root ganglia (DRG, T13 to L2) were identified for patch clamp and gene expression studies. Referred visceral sensitivity was assessed by measuring withdrawal response to stimulation by von Frey filaments (VFF) in the lower abdomen. Membrane excitability of colon-projecting DRG neurons was significantly enhanced, and the withdrawal response to VFF stimulation markedly increased in BO rats. The expression of NGF mRNA and protein was increased in a time-dependent manner (day 1 to day 7) in colonic SMC, but not in mucosa/submucosa of the obstructed colon. Mechanical stretch in vitro caused robust NGF mRNA and protein expression in colonic SMC. Treatment with anti-NGF antibody attenuated colon neuron hyper-excitability and referred hypersensitivity in BO rats. Obstruction led to significant increases of tetrodotoxin-resistant (TTX-r) Na+ currents and mRNA expression of Nav1.8, but not Nav1.6 and Nav1.7 in colon neurons; these changes were abolished by anti-NGF treatment. In conclusion, mechanical stress-induced upregulation of NGF in colon SMC underlies the visceral hypersensitivity in BO through increased gene expression and activity of TTX-resistant Na+ channels in sensory neurons.

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Altered production of nerve growth factor in aganglionic intestines

Cited by 23 publications

References 13 publications

Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

Hypertrophy of Neurons Within Cardiac Ganglia in Human, Canine, and Rat Heart Failure: The Potential Role of Nerve Growth Factor

SOX10is abnormally expressed in aganglionic bowel of Hirschsprung's disease infants

Pathogenesis of abdominal pain in bowel obstruction: role of mechanical stress-induced upregulation of nerve growth factor in gut smooth muscle cells

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