Structural Abnormalities of the Myenteric (Auerbach's) Plexus in Familial Dysautonomia (Riley-Day Syndrome) as Demonstrated by Flat-Mount Preparation of the Esophagus and Stomach

Ariel, liana; Wells, Theadis R.

doi:10.3109/15513818509025906

Cited by 11 publications

(4 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While it is well known that FD patients suffer from frequent GI dysfunction 17 , at least one imaging study found delayed esophageal transit times and delayed gastric emptying among FD patients compared to healthy control subjects, implicating a dysfunctional myenteric plexus of the upper GI tract in FD 42 . These results are consistent with two case studies that isolated and visually compared the esophageal, gastric and/or appendiceal myenteric plexus of FD patients and age-matched control subjects 43 ; these studies showed significant reductions in the neuronal number and/or ganglion complexity. Collectively, these results suggest that dysfunctional gut motility in FD patients is most likely due to alterations in neuronal density throughout the GI tract.…”

Section: Discussionsupporting

confidence: 90%

Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia

et al. 2023

View full text Add to dashboard Cite

Familial dysautonomia (FD) is a rare genetic neurologic disorder caused by impaired neuronal development and progressive degeneration of both the peripheral and central nervous systems. FD is monogenic, with >99.4% of patients sharing an identical point mutation in the elongator acetyltransferase complex subunit 1 (ELP1) gene, providing a relatively simple genetic background in which to identify modifiable factors that influence pathology. Gastrointestinal symptoms and metabolic deficits are common among FD patients, which supports the hypothesis that the gut microbiome and metabolome are altered and dysfunctional compared to healthy individuals. Here we show significant differences in gut microbiome composition (16 S rRNA gene sequencing of stool samples) and NMR-based stool and serum metabolomes between a cohort of FD patients (~14% of patients worldwide) and their cohabitating, healthy relatives. We show that key observations in human subjects are recapitulated in a neuron-specific Elp1-deficient mouse model, and that cohousing mutant and littermate control mice ameliorates gut microbiome dysbiosis, improves deficits in gut transit, and reduces disease severity. Our results provide evidence that neurologic deficits in FD alter the structure and function of the gut microbiome, which shifts overall host metabolism to perpetuate further neurodegeneration.

show abstract

Section: Discussionsupporting

confidence: 90%

Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia

et al. 2023

View full text Add to dashboard Cite

show abstract

“…It should be noted that our conclusions are based on observations on the appendix because specimens of upper gastrointestinal tract from FD patients are not available. However, our results are in accordance with a study on the esophagus and stomach from FD patients [18], and are thus likely to represent, at least qualitatively, other regions of the digestive system.…”

Section: Discussionsupporting

confidence: 93%

“…Two studies, each on a single patient, revealed no histological changes in myenteric neurons [20,22], and in another work on a single patient, some abnormalities in these neurons were noticed [21]. The most recent study dealing with the innervation of the gastrointestinal tract of FD patients was published back in 1985 [18]. In that study, which included only three patients, two patients demonstrated morphologic differences of the esophageal and gastric myenteric plexuses, using flat mount preparations.…”

Section: Discussionmentioning

confidence: 97%

Decreased density of ganglia and neurons in the myenteric plexus of familial dysautonomia patients

Bar-Shai

Maayan

Vromen

et al. 2004

Journal of the Neurological Sciences

View full text Add to dashboard Cite

“…Abnormality in the relative numbers of different transmitter-secreting neurons in the This paper presents the results of preliminary studies of the structure of the Auerbach plexus in a variety of genetic disorders. Ariel and Wells, 1985;Nakazato et al, 19861. Weinberg, 1975;Emery et al, 1967;Ariel and Wells, 19851.…”

Section: Introductionmentioning

confidence: 99%

Demonstration of myenteric plexus abnormalities in genetic diseases by a microdissection technique: Preliminary studies

et al. 1987

Self Cite

View full text Add to dashboard Cite

Eighty‐eight specimens of esophagus, small intestine, or colon from 45 patients, predominantly infants and children, with 30 different genetic diseases were analyzed by a microdissection technique for the following abnormalities of the Aucrbach (myenteric) plexus: (1) abnormality of the pattern of the nervous network of the plexus, (2) abnormal fraction of neural tissue in the plane of the plexus, (3) abnormal size or appearance of the cytoplasm of the neurons of the plexus, and (4) abnormal number of neurons in the ganglia of the plexus. Seven of 8 specimens of esophagus from patients with neuronal storage diseases (infantile Niemann‐Pick disease, Jansky‐Bielschowsky disease, etc.) showed an increased fraction of neural tissue in the plane of the plexus, whereas 2 of 3 patients with Cockayne syndrome showed a reduced fraction, with abnormally slender interganglionic fibers. The fraction of neural tissue in the plane of the plexus was also abnormal at one or more levels in patients with adrenoleukodystrophy, ataxia telangiectasia, Krabbe disease, and juvenile metachromatic leukodystrophy. Abnormality of neuron size and cytology was seen in several neuronal lipidoses, including Jansky‐Bielschowsky and Sandhoff diseases and juvenile GM2 gangliosidosis, with the most striking neuronal enlargement noted in infantile Niemann‐Pick disease. Abnormalities of plexus mass or pattern, as well as those of neuronal cytoplasm and neuron number, offer improved insight into possible mechanisms producing gastrointestinal tract dysfunction (swallowing difficulty, gastroesophageal reflux, constipation, etc) in patients with genetic disorders.

show abstract

Structural Abnormalities of the Myenteric (Auerbach's) Plexus in Familial Dysautonomia (Riley-Day Syndrome) as Demonstrated by Flat-Mount Preparation of the Esophagus and Stomach

Cited by 11 publications

References 11 publications

Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia

Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia

Decreased density of ganglia and neurons in the myenteric plexus of familial dysautonomia patients

Demonstration of myenteric plexus abnormalities in genetic diseases by a microdissection technique: Preliminary studies

Contact Info

Product

Resources

About