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Journal of Neurogastroenterology and... Oct 2023Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and...
BACKGROUND/AIMS
Multiple sclerosis (MS) is an inflammatory disease characterized by the demyelination of primarily the central nervous system. Diffuse esophageal spasm (DES) and achalasia are both disorders of esophageal peristalsis which cause clinical symptoms of dysphagia. Mechanisms involving dysfunction of the pre- and post-ganglionic nerve fibers of the myenteric plexus have been proposed. We sought to determine whether MS confers an increased risk of developing achalasia or DES.
METHODS
Cohort analysis was done using the Explorys database. Univariate logistic regression was performed to determine the odds MS confers to each motility disorder studied. Comparison of proportions of dysautonomia comorbidities was performed among the cohorts. Patients with a prior diagnosis of diabetes mellitus, chronic Chagas' disease, opioid use, or CREST syndrome were excluded from the study.
RESULTS
Odds of MS patients developing achalasia or DES were (OR, 2.09; 95% CI, 1.73-2.52; < 0.001) and (OR, 3.15; 95% CI, 2.89-3.42; < 0.001), respectively. In the MS/achalasia cohort, 27.27%, 18.18%, 9.09%, and 45.45% patients had urinary incontinence, gastroparesis, impotence, and insomnia, respectively. In the MS/DES cohort, 35.19%, 11.11%, 3.70%, and 55.56% had these symptoms. In MS patients without motility disorders, 12.64%, 0.79%, 2.21%, and 21.85% had these symptoms.
CONCLUSIONS
Patients with MS have higher odds of developing achalasia or DES compared to patients without MS. MS patients with achalasia or DES have higher rates of dysautonomia comorbidities. This suggests that these patients have a more severe disease phenotype in regards to the extent of neuronal degradation and demyelination causing the autonomic dysfunction.
PubMed: 37528077
DOI: 10.5056/jnm22173 -
Biomolecules Jun 2023Mutations in the Neuroligin-3 () gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction, but cellular expression in the enteric...
Quantitative Spatial Analysis of Neuroligin-3 mRNA Expression in the Enteric Nervous System Reveals a Potential Role in Neuronal-Glial Synapses and Reduced Expression in Mice.
Mutations in the Neuroligin-3 () gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction, but cellular expression in the enteric nervous system remains to be characterised. We combined RNAScope in situ hybridization and immunofluorescence to measure mRNA expression in cholinergic and VIP-expressing submucosal neurons, nitrergic and calretinin-containing myenteric neurons and glial cells in both WT and mutant mice. We measured mRNA neuronal and glial expression via quantitative three-dimensional image analysis. To validate dual RNAScope/immunofluorescence data, we interrogated available single-cell RNA sequencing (scRNASeq) data to assess for , , and their binding partners, , and , in enteric neural subsets. Most submucosal and myenteric neurons expressed mRNA. In contrast to other and binding partners, was strongly expressed in enteric glia, suggesting a role for neuroligin-3 in mediating enteric neuron-glia interactions. The autism-associated R451C mutation reduces mRNA expression in cholinergic but not in VIPergic submucosal neurons. In the myenteric plexus, mRNA levels are reduced in calretinin, nNOS-labelled neurons and S100 β -labelled glia. We provide a comprehensive cellular profile for neuroligin-3 expression in ileal neuronal subpopulations of mice expressing the R451C autism-associated mutation in which may contribute to the understanding of the pathophysiology of GI dysfunction in ASD.
Topics: Mice; Animals; Calbindin 2; Autism Spectrum Disorder; Neurons; Neuroglia; Enteric Nervous System; Synapses; Cholinergic Agents
PubMed: 37509099
DOI: 10.3390/biom13071063 -
The American Surgeon Nov 2023Eosinophilic myenteric ganglionitis (EMG) is a rare pathologic finding within the Auerbach myenteric plexus characterized by eosinophilic infiltration on light...
Eosinophilic myenteric ganglionitis (EMG) is a rare pathologic finding within the Auerbach myenteric plexus characterized by eosinophilic infiltration on light microscopy. The plexus's ultimate obliteration results in chronic intestinal pseudo-obstruction (CIPO). EMG is almost exclusively seen in the pediatric population. The diagnosis of EMG is made through full-thickness rectal biopsy and EMG is not detectable through routine screening measures such as imaging or colonoscopy. The current treatment modality for this disorder is not standardized, and has often been treated with systemic steroids given its eosinophilic involvement. This case presents a 73-year-old male with chronic constipation presenting with new obstipation in the setting of recent orthopedic intervention requiring outpatient opioids. Admission radiographs were consistent with sigmoid volvulus. Following endoscopic detorsion, exploratory laparotomy revealed diffuse colonic dilation and distal ischemia requiring a Hartmann's procedure. Surgical pathology revealed EMG, increasing the complexity of subsequent surgical decision-making after his urgent operation.
Topics: Male; Humans; Child; Aged; Intestinal Volvulus; Colon; Intestinal Pseudo-Obstruction; Myenteric Plexus; Colonoscopy; Sigmoid Diseases
PubMed: 37501639
DOI: 10.1177/00031348231191198 -
Neurogastroenterology and Motility Nov 2023Neurogenic bowel is a dysmotility disorder following spinal cord injury (SCI) that negatively impacts quality of life, social integration, and physical health. Colonic...
BACKGROUND
Neurogenic bowel is a dysmotility disorder following spinal cord injury (SCI) that negatively impacts quality of life, social integration, and physical health. Colonic transit is directly modulated by the enteric nervous system. Interstitial Cells of Cajal (ICC) distributed throughout the small intestine and colon serve as specialized pacemaker cells, generating rhythmic electrical slow waves within intestinal smooth muscle, or serve as an interface between smooth muscle cells and enteric motor neurons of the myenteric plexus. Interstitial Cells of Cajal loss has been reported for other preclinical models of dysmotility, and our previous experimental SCI study provided evidence of reduced excitatory and inhibitory enteric neuronal count and smooth muscle neural control.
METHODS
Immunohistochemistry for the ICC-specific marker c-Kit was utilized to examine neuromuscular remodeling of the distal colon in male and female rats with experimental SCI.
KEY RESULTS
Myenteric plexus ICC (ICC-MP) exhibited increased cell counts 3 days following SCI in male rats, but did not significantly increase in females until 3 weeks after SCI. On average, ICC-MP total primary arborization length increased significantly in male rats at 3-day, 3-week, and 6-week time points, whereas in females, this increase occurred most frequently at 6 weeks post-SCI. Conversely, circular muscle ICC (ICC-CM) did not demonstrate post-SCI changes.
CONCLUSIONS AND INFERENCES
These data demonstrate resiliency of the ICC-MP in neurogenic bowel following SCI, unlike seen in other related disease states. This plasticity underscores the need to further understand neuromuscular changes driving colonic dysmotility after SCI in order to advance therapeutic targets for neurogenic bowel treatment.
Topics: Rats; Male; Female; Animals; Neurogenic Bowel; Quality of Life; Enteric Nervous System; Myenteric Plexus; Colon; Motor Neurons; Spinal Cord Injuries
PubMed: 37480186
DOI: 10.1111/nmo.14646 -
Anatomia, Histologia, Embryologia Nov 2023Rabbit large intestine has a segment-specific morphology and motility. However, the morphological features of the myenteric plexus, which controls intestinal motility,...
Rabbit large intestine has a segment-specific morphology and motility. However, the morphological features of the myenteric plexus, which controls intestinal motility, have not been characterized in each large intestinal segment. We investigated the myenteric plexus morphology in the rabbit large intestine using protein gene product 9.5 immunohistochemistry in whole-mount preparations. The tenial part of the first and second segments of the proximal colon had the most well developed myenteric plexus, while the caecum had the least. These findings suggest different neuronal control over the motility of each intestinal segment, thereby providing a fundamental understanding of the rabbit enteric nervous system.
Topics: Rabbits; Animals; Myenteric Plexus; Intestine, Large; Intestines; Enteric Nervous System; Neurons
PubMed: 37458241
DOI: 10.1111/ahe.12950 -
Animals : An Open Access Journal From... Jun 2023Energy deficiency causes multiple organ dysfunctions after LPS induction. Quercetin is a phenolic compound found in herbal medicines. However, the effects of quercetin...
Energy deficiency causes multiple organ dysfunctions after LPS induction. Quercetin is a phenolic compound found in herbal medicines. However, the effects of quercetin in alleviating LPS-induced energy deficiency remain unclear. In the present study, an in vivo LPS-induced inflammation model was established in chicken embryos. Specific pathogen-free chicken embryos (n = 120) were allocated to control, PBS with or without ethanol, quercetin (10, 20, or 40 nmol, respectively), and LPS (125 ng/egg) with or without quercetin groups. Fifteen day old embryonated eggs were injected with the abovementioned solutions via the allantoic cavity. On embryonic day 19, the tissues of the embryos were collected for histopathological examination using frozen oil red O staining, RNA extraction, real-time quantitative polymerase chain reaction, and immunohistochemical investigations. The glycogen and lipid contents in the liver increased after LPS stimulation as compared with the PBS group, whereas quercetin decreased the accumulation as compared with the LPS group. The mRNA expressions of AMPKα1 and AMPKα2 in the duodena, ceca, and livers were upregulated after LPS induction as compared with the PBS group, while quercetin could downregulate these expressions as compared with the LPS group. The immunopositivity of AMPKα2 in the villus, crypt, lamina propria, tunica muscularis, and myenteric plexus in the duodena and in the cytoplasms of hepatocytes significantly increased after LPS induction when compared with the PBS group ( < 0.01), whereas the immunopositivity to AMPKα2 in the quercetin treatment group significantly decreased when compared with the LPS group ( < 0.01 or < 0.05). The LPS-induced high expressions of transcription factor PPARα and glucose transporter (SGLT1) were blocked by quercetin in the duodena, ceca, and livers. Quercetin treatment improved the LPS-induced decrease in APOA4 in the duodena, ceca, and livers. The mRNA expression of PEPT1 in the duodena and ceca increased after LPS challenge, whereas quercetin could downregulate PEPT1 gene expression. These data demonstrate that quercetin improved the energy deficiency induced by LPS in chicken embryos. The LPS-induced inflammation model was established to avoid the effect of LPS exposure from the environment and intestinal flora. The results form the basis the administration of quercetin pretreatment (in ovo infection) to improve the energy state of chicken embryos and improve the inflammation response.
PubMed: 37443849
DOI: 10.3390/ani13132051 -
Translational Pediatrics Jun 2023Hypoganglionosis resembles Hirschsprung's disease as in both diseases, patients may present with severe constipation or pseudo-obstruction. To date, diagnosis of...
BACKGROUND
Hypoganglionosis resembles Hirschsprung's disease as in both diseases, patients may present with severe constipation or pseudo-obstruction. To date, diagnosis of hypoganglionosis is still difficult to be established due to lack of international consensus regarding diagnostic criteria. This study aims to evaluate the use of immunohistochemistry to provide objective support for our initial subjective impression of hypoganglionosis as well as to describe the morphological features of this study.
METHODS
This is a cross-sectional study. Three resected intestinal samples from patients with hypoganglionosis at Kyushu University Hospital, Fukuoka, Japan were included in this study. One healthy intestinal sample was used as control. All specimens were immunohistochemically stained with anti-S-100 protein, anti-α-smooth muscle actin (α-SMA), and anti-c-kit protein antibodies.
RESULTS
(I) S-100 immunostaining: hypoplasia of the myenteric ganglia and marked reduction of intramuscular nerve fibers were observed in several segments of the intestine. (II) α-SMA immunostaining: the pattern of the muscular layers was almost normal in all segments; however, some areas showed hypotrophy of the circular muscle (CM) layers and hypertrophy of the longitudinal muscle (LM) layers. (III) C-kit immunostaining: a decreased in the number of interstitial cells of Cajal (ICCs) was observed in almost all segments of the resected intestine, even around the myenteric plexus.
CONCLUSIONS
Each segment of intestine in hypoganglionosis had different numbers of ICCs, sizes, and distributions of ganglions, as well as patterns of musculature, which may range from severely abnormal to nearly normal. Further investigations regarding the definition, etiology, diagnosis, and treatment of this disease should be performed to improve the prognosis of this disease.
PubMed: 37427059
DOI: 10.21037/tp-22-592 -
Folia Medica Cracoviensia Apr 2023Anorexia nervosa (AN) is an eating disorder characterized by distinct etiopathogenetic concepts that are gradually being linked together to unravel the dominant...
Anorexia nervosa (AN) is an eating disorder characterized by distinct etiopathogenetic concepts that are gradually being linked together to unravel the dominant pathophysiological pathways underlying the disease. Excessive food restrictions, often accompanied by over-exercise and undertaken to lose weight, lead to the development of numerous complications. The biological concept of neurohormonal dysfunction in AN seems incomplete without demonstrating or excluding the role of the enteric nervous system (ENS). Using an animal model of activity-based anorexia (ABA), we conducted the preliminary assessment of the ENS structure. Here we show, in preparations stained by immunohistochemistry with anti- ChAT, anti-NOS, anti-PGP 9.5, anti-c-fos, and anti-TH antibodies, a lower density of cholinergic and nitrergic nerve fibers as well as reduced neuronal activity in myenteric plexus. Such structural and functional damage to the ENS may be responsible for a number of gastrointestinal symptoms that worsen the course of the disease. In addition, we expanded the study to address the unresolved issue of mechanical and thermal pain sensitivity in AN. The Von Frey and hot plate tests revealed, that in ABA animals, the pain threshold for mechanical stimulus decreases while for thermal increases. In this way, we have significantly supplemented the background of AN with potentially observable nervous system changes which may influence the evolution of the therapeutic approach in the future.
Topics: Animals; Anorexia; Enteric Nervous System; Pain Perception; Models, Animal; Pain
PubMed: 37406277
DOI: 10.24425/fmc.2023.145430 -
Histochemistry and Cell Biology Nov 2023Short bowel syndrome (SBS) is a severe, life-threatening condition and one of the leading causes of intestinal failure in children. Here we were interested in changes in...
Short bowel syndrome (SBS) is a severe, life-threatening condition and one of the leading causes of intestinal failure in children. Here we were interested in changes in muscle layers and especially in the myenteric plexus of the enteric nervous system (ENS) of the small bowel in the context of intestinal adaptation. Twelve rats underwent a massive resection of the small intestine to induce SBS. Sham laparotomy without small bowel transection was performed in 10 rats. Two weeks after surgery, the remaining jejunum and ileum were harvested and studied. Samples of human small bowel were obtained from patients who underwent resection of small bowel segments due to a medical indication. Morphological changes in the muscle layers and the expression of nestin, a marker for neuronal plasticity, were studied. Following SBS, muscle tissue increases significantly in both parts of the small bowel, i.e., jejunum and ileum. The leading pathophysiological mechanism of these changes is hypertrophy. Additionally, we observed an increased nestin expression in the myenteric plexus in the remaining bowel with SBS. Our human data also showed that in patients with SBS, the proportion of stem cells in the myenteric plexus had risen by more than twofold. Our findings suggest that the ENS is tightly connected to changes in intestinal muscle layers and is critically involved in the process of intestinal adaptation to SBS.
Topics: Child; Rats; Humans; Animals; Short Bowel Syndrome; Nestin; Rats, Sprague-Dawley; Ileum; Disease Models, Animal; Neuronal Plasticity
PubMed: 37395792
DOI: 10.1007/s00418-023-02214-4 -
Neurogastroenterology and Motility Sep 2023In this prospective cohort study, we evaluated features of "adult-onset megacolon with focal hypoganglionosis."
BACKGROUND
In this prospective cohort study, we evaluated features of "adult-onset megacolon with focal hypoganglionosis."
METHODS
We assessed the radiologic, endoscopic, and histopathologic phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology.
KEY RESULTS
The median age of the patients with adult-onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0-74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval [CI], 72-86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range [IQR], 3.7-16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190-338) in the proximal and 95 cells/cm (IQR, 45-213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment [change in the Global Bowel Satisfaction score, -5.4 points (surgery) vs. -0.3 points (medical treatment); p < 0.001].
CONCLUSIONS AND INFERENCES
Adult-onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients.
Topics: Humans; Adult; Middle Aged; Aged; Prospective Studies; Megacolon; Colon; Myenteric Plexus; Colectomy
PubMed: 37392417
DOI: 10.1111/nmo.14630