Quantification and neurochemical coding of the myenteric plexus in humans: No regional variation between the distal colon and rectum

Ng, Kheng‐Seong; Montes-Adrian, Noemi A; Mahns, David A.; Gladman, Marc A.

doi:10.1111/nmo.13193

Cited by 11 publications

(12 citation statements)

References 34 publications

(96 reference statements)

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“…Since descending motor neurons (which are mostly inhibitory motor neurons) are rarely immunoreactive for ChAT, 3 it is likely that all ChAT+/NOS+ neurons are descending interneurons. A population of ChAT+/NOS+ cells has been reported by several groups studying human colon with multiple labeling immunohistochemistry; estimates range from 3%‐10% of all myenteric neurons 33‐35 . Some of these are likely to correspond to the NOS‐immunoreactive, 5‐HT containing cells, since all 5‐HT neurons in small intestine 18 and large intestine of guinea pig colon 27 are ChAT immunoreactive and 5‐HT cells in these species all have long descending projections 36 …”

Section: Discussionmentioning

confidence: 93%

“…A population of ChAT+/NOS+ cells has been reported by several groups studying human colon with multiple labeling immunohistochemistry; estimates range from 3%-10% of all myenteric neurons. [33][34][35] Some of these are likely to correspond to the NOS-immunoreactive, 5-HT containing cells, since all 5-HT neurons in small intestine 18 and large intestine of guinea pig colon 27 are ChAT immunoreactive and 5-HT cells in these species all have long descending projections. 36 Putting these data together, the populations of long descend-…”

Section: Long Descending Pathwaysmentioning

confidence: 99%

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Characterization of putative interneurons in the myenteric plexus of human colon

Humenick

Chen

Wattchow

et al. 2020

Neurogastroenterology Motil

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Background: The enteric nervous system contains multiple classes of neurons, distinguishable by morphology, immunohistochemical markers, and projections; however, specific combinations differ between species. Here, types of enteric neurons in human colon were characterized immunohistochemically, using retrograde tracing combined with multiple labeling immunohistochemistry, focussing on non-motor neurons. Methods: The fluorescent carbocyanine tracer, DiI, was applied to the myenteric plexus in ex vivo preparations, filling neurons projecting within the plexus. Limits of projection lengths of motor neurons were established, allowing them to be excluded from the analysis. Long ascending and descending interneurons were then distinguished by labeling for discriminating immunohistochemical markers: calbindin, calretinin, enkephalin, 5-hydroxytryptamine, nitric oxide synthase, and substance P. These results were combined with a previous published study in which nitric oxide synthase and choline acetyltransferase immunoreactivities were established. Key Results: Long ascending neurons (with projections longer than 8 mm, which excludes more than 95% motor neurons) formed four types, in descending order of abundance, defined by immunoreactivity for: (a) ChAT+/ENK+, (b) ChAT+/ENK+/ SP+, (c) ChAT+/Calb+, and (d) ChAT+/ENK+/Calb+. Long descending neurons, up to 70 mm long also formed at least four types, distinguished by immunoreactivity for (a) NOS + cells (without ChAT), (b) ChAT+/NOS+, (c) ChAT+/Calret+, and (d) ChAT+/5HT + cells (with or without NOS). Conclusions and Inferences: Long interneurons, which do not innervate muscularis externa, are likely to coordinate neural activity over distances of many centimeters along the colon. Characterizing their neurochemical coding provides a basis for understanding their roles, investigating their connectivity, and building a comprehensive account of human colonic enteric neurons.

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Section: Discussionmentioning

confidence: 93%

Section: Long Descending Pathwaysmentioning

confidence: 99%

Characterization of putative interneurons in the myenteric plexus of human colon

Humenick

Chen

Wattchow

et al. 2020

Neurogastroenterology Motil

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“…Types of innervation that have been described include cholinergic excitation, purinergic excitatory, and peptidergic inhibitory mediated by VIP (). The present study distinguished excitatory neurons by their immunoreactivity for choline acetyltransferase, the rate‐limiting step for synthesis of acetylcholine, using an antiserum previously characterized in human gastrointestinal tract which labels similar proportions of cholinergic neurons in human colon as a commercial antiserum . However, because DiI is highly soluble in ethanol, DMSO, and detergents, glycerol was used in the present study to permeabilize tissue for immunohistochemistry .…”

Section: Discussionmentioning

confidence: 99%

“…The present study distinguished excitatory neurons by their immunoreactivity for choline acetyltransferase, the rate-limiting step for synthesis of acetylcholine, 31 using an antiserum previously characterized in human gastrointestinal tract 32 which labels similar proportions of cholinergic neurons in human colon as a commercial antiserum. 33,34 However, because…”

Section: Discussionmentioning

confidence: 99%

Characterization of projections of longitudinal muscle motor neurons in human colon

Humenick

Chen

Lauder

et al. 2019

Neurogastroenterology Motil

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Background The enteric nervous system contains inhibitory and excitatory motor neurons which modulate smooth muscle contractility. Cell bodies of longitudinal muscle motor neurons have not been identified in human intestine. Methods We used retrograde tracing ex vivo with DiI, with multiple labeling immunohistochemistry, to characterize motor neurons innervating tenial and inter‐tenial longitudinal muscle of human colon. Key Results The most abundant immunohistochemical markers in the tertiary plexus were vesicular acetylcholine transporter, nitric oxide synthase (NOS), and vasoactive intestinal polypeptide (VIP). Of retrogradely traced motor neurons innervating inter‐tenial longitudinal muscle, 95% were located within 6mm oral or anal to the DiI application site. Excitatory motor neuron cell bodies, immunoreactive for choline acetyltransferase (ChAT), were clustered aborally, whereas NOS‐immunoreactive cell bodies were distributed either side of the DiI application site. Motor neurons had small cell bodies, averaging 438 + 18µm2 in cross‐sectional area, similar for ChAT‐ and NOS‐immunoreactive subtypes. Motor neurons innervating the tenia had slightly longer axial projections, with 95% located within 9mm. ChAT‐immunoreactive excitatory motor neurons to tenia were clustered aborally, whereas NOS‐immunoreactive inhibitory motor neurons had both ascending and descending projections. VIP immunoreactivity was rarely present without NOS immunoreactivity in motor neurons. Conclusions and Inferences Tenial and inter‐tenial motor neurons innervating the longitudinal muscle have short projections. Inhibitory motor neurons have less polarized projections than cholinergic excitatory motor neurons. Longitudinal and circular muscle layers are innervated by distinct local populations of excitatory and inhibitory motor neurons. A population of human enteric neurons that contribute significantly to colonic motility has been characterized.

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“…Slow transit constipation (STC) is caused by a disorder in colon transmission, and it is characterized by symptoms including infrequent and difficult defecation, accompanying with a sensation of incomplete bowel evacuation. The prevalence of STC in chronic constipation is about 46 % [2]. The cure rate is low due to persistence of the clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

Effect of atractylenolide III on interstitial cells of Cajal and C-kit/SCF pathway of rats with loperamide-induced slow transit constipation

Wang¹,

Yuxia²,

Li³

et al. 2021

Trop. J. Pharm Res

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Purpose: To determine the effect of atractylenolide-III (ATL-III) on loperamide-induced slow transit constipation (STC) in a rat STC model, and to elucidate the mechanisms involved. Methods: Male Wistar rats were divided into five groups (n=6 per group): normal control group (NG), model group, and three STC rat groups treated with different doses of ATL-III, viz, 5, 10 and 15 mg/kg. The rats were treated for 15 days. Feed consumption, fecal excretion and intestinal transit rate were determined. Nitric oxide synthase (NOS), somatostatin (SS), serotonin (5-HT), and vasoactive intestinal peptide (VIP) were measured with enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expressions of C-kit, SCF, PKC, and PI-3K were assayed using Western blot analysis and realtime reverse transcription polymerase chain reaction (RT-PCR), respectively. Results: The amount, weight, and moisture content of stool, and water consumption were significantly higher in ATL-III-treated groups than in the untreated (model) group (p < 0.05), whereas no difference was observed in feed intake. Intestinal transit rate was higher in the ATL-III-treated groups (p < 0.05). Decreased NOS, SS and VIP levels and increased 5-HT level were seen in the ATL-III-treated groups (p < 0.05). ATL-III treatment also induced increases in smooth muscle cells, neuronal cells, and mucous layer (p<0.05). Results from RT-PCR and Western blot revealed that ATL-III–treated groups had elevated c-kit, SCF, PKC, as well as PI-3K mRNA and protein expressions (p < 0.05). Conclusion: These results suggest that ATL-III mitigates loperamide-induced STC in rats via stimulation of NOS, SS, VIP, and 5-HT secretions. It also increases smooth muscle cells, neuronal cells, and mucous layer, and regulates the signaling pathways involving PKC, PI3K, SCF, and c-kit.

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Quantification and neurochemical coding of the myenteric plexus in humans: No regional variation between the distal colon and rectum

Cited by 11 publications

References 34 publications

Characterization of putative interneurons in the myenteric plexus of human colon

Characterization of putative interneurons in the myenteric plexus of human colon

Characterization of projections of longitudinal muscle motor neurons in human colon

Effect of atractylenolide III on interstitial cells of Cajal and C-kit/SCF pathway of rats with loperamide-induced slow transit constipation

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