scholarly journals Antibiotic exposure postweaning disrupts the neurochemistry and function of enteric neurons mediating colonic motor activity

2020 ◽  
Vol 318 (6) ◽  
pp. G1042-G1053 ◽  
Author(s):  
Lin Y. Hung ◽  
Pavitha Parathan ◽  
Prapaporn Boonma ◽  
Qinglong Wu ◽  
Yi Wang ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Colonic Motility ◽  
Enteric Neurons ◽  
Reporter Mice ◽  
Colonic Motor ◽  
Rdna Sequencing ◽  
Colonic Motor Activity ◽  
Physiological Impact ◽  
And Function ◽  
Serotonin Biosynthesis

The period during and immediately after weaning is an important developmental window when marked shifts in gut microbiota can regulate the maturation of the enteric nervous system (ENS). Because microbiota-derived signals that modulate ENS development are poorly understood, we examined the physiological impact of the broad spectrum of antibiotic, vancomycin-administered postweaning on colonic motility, neurochemistry of enteric neurons, and neuronal excitability. The functional impact of vancomycin on enteric neurons was investigated by Ca2+ imaging in Wnt1-Cre;R26R-GCaMP3 reporter mice to characterize alterations in the submucosal and the myenteric plexus, which contains the neuronal circuitry controlling gut motility. 16S rDNA sequencing of fecal specimens after oral vancomycin demonstrated significant deviations in microbiota abundance, diversity, and community composition. Vancomycin significantly increased the relative family rank abundance of Akkermansiaceae, Lactobacillaceae, and Enterobacteriaceae at the expense of Lachnospiraceae and Bacteroidaceae. In sharp contrast to neonatal vancomycin exposure, microbiota compositional shifts in weaned animals were associated with slower colonic migrating motor complexes (CMMCs) without mucosal serotonin biosynthesis being altered. The slowing of CMMCs is linked to disruptions in the neurochemistry of the underlying enteric circuitry. This included significant reductions in cholinergic and calbindin+ myenteric neurons, neuronal nitric oxide synthase+ submucosal neurons, neurofilament M+ enteric neurons, and increased proportions of cholinergic submucosal neurons. The antibiotic treatment also increased transmission and responsiveness in myenteric and submucosal neurons that may enhance inhibitory motor pathways, leading to slower CMMCs. Differential vancomycin responses during neonatal and weaning periods in mice highlight the developmental-specific impact of antibiotics on colonic enteric circuitry and motility.

Role of adipokines in regulation of colonic motor activity in overweight and obese individuals

2021 ◽  
pp. 48-51
Author(s):  
М. М. Fedorin ◽  
M. A. Livzan ◽  
O. V. Gaus
Keyword(s):  
Literature Search ◽  
Colonic Motility ◽  
Gastrointestinal Hormones ◽  
Colonic Motor ◽  
Motility Regulation ◽  
Colonic Motor Activity ◽  
And Function ◽  
Overweight Or Obesity ◽  
Key Words Colon

The increasing proportion of the population suffering from overweight or obesity is now taking on the character of a pandemic. In the literature, there have begun to appear reports of associations in individuals with impaired colonic motility and a body mass index above 25 kg/m2. The present publication was prepared to systematize data on possible mechanisms of colonic motility disorders in overweight and obese individuals, including through changes in adipokine secretion and function. The literature search was performed in Embase, PubMed, and Google Scholar, using the key words ‘colon motility regulation’, ‘adipokines’, ‘gastrointestinal hormones’, ‘intestinal microbiota’, ‘overweight’, ‘obesity’, ‘visceral fat’.

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

scholarly journals Brain Long Noncoding RNAs: Multitask Regulators of Neuronal Differentiation and Function

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3951
Author(s):  
Sarva Keihani ◽  
Verena Kluever ◽  
Eugenio F. Fornasiero
Keyword(s):  
Neuronal Differentiation ◽  
Neuronal Excitability ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Regulatory Mechanisms ◽  
Control Robustness ◽  
Living Organisms ◽  
And Function ◽  
Regulatory Functions ◽  
Neuronal Physiology

The extraordinary cellular diversity and the complex connections established within different cells types render the nervous system of vertebrates one of the most sophisticated tissues found in living organisms. Such complexity is ensured by numerous regulatory mechanisms that provide tight spatiotemporal control, robustness and reliability. While the unusual abundance of long noncoding RNAs (lncRNAs) in nervous tissues was traditionally puzzling, it is becoming clear that these molecules have genuine regulatory functions in the brain and they are essential for neuronal physiology. The canonical view of RNA as predominantly a ‘coding molecule’ has been largely surpassed, together with the conception that lncRNAs only represent ‘waste material’ produced by cells as a side effect of pervasive transcription. Here we review a growing body of evidence showing that lncRNAs play key roles in several regulatory mechanisms of neurons and other brain cells. In particular, neuronal lncRNAs are crucial for orchestrating neurogenesis, for tuning neuronal differentiation and for the exact calibration of neuronal excitability. Moreover, their diversity and the association to neurodegenerative diseases render them particularly interesting as putative biomarkers for brain disease. Overall, we foresee that in the future a more systematic scrutiny of lncRNA functions will be instrumental for an exhaustive understanding of neuronal pathophysiology.

scholarly journals Effects of a 5-hydroxytryptamine3 receptor antagonist (ICS 205-930) on colonic motor activity in healthy men.

1989 ◽  
Vol 28 (3) ◽  
pp. 315-322 ◽  
Author(s):  
G. Stacher ◽  
G. Gaupmann ◽  
C. Schneider ◽  
G. Stacher-Janotta ◽  
G. Steiner-Mittelbach ◽  
...  
Keyword(s):  
Motor Activity ◽  
Receptor Antagonist ◽  
Healthy Men ◽  
Colonic Motor ◽  
Colonic Motor Activity ◽  
Ics 205 930

scholarly journals Effect of Motilin on Colonic Motor Activity in the Interdigestive State in Conscious Dogs.

1995 ◽  
Vol 176 (1) ◽  
pp. 53-60 ◽  
Author(s):  
CHIKASHI SHIBATA ◽  
IWAO SASAKI ◽  
HIROO NAITO ◽  
MICHINAGA TAKAHASHI ◽  
TAKASHI DOI ◽  
...  
Keyword(s):  
Motor Activity ◽  
Conscious Dogs ◽  
Colonic Motor ◽  
Colonic Motor Activity

5-Hydroxytryptophan activates colonic myenteric neurons and propulsive motor function through 5-HT4 receptors in conscious mice

2007 ◽  
Vol 292 (1) ◽  
pp. G419-G428 ◽  
Author(s):  
L. Wang ◽  
V. Martínez ◽  
H. Kimura ◽  
Y. Taché
Keyword(s):  
Motor Function ◽  
Colonic Motility ◽  
Distal Colon ◽  
Nadph Diaphorase ◽  
Maximal Response ◽  
Myenteric Neurons ◽  
Diaphorase Activity ◽  
Colonic Motor ◽  
Different Populations ◽  
Fos Expression

Serotonin [5-hydroxytryptamine (5-HT)] acts as a modulator of colonic motility and secretion. We characterized the action of the 5-HT precursor 5-hydroxytryptophan (5-HTP) on colonic myenteric neurons and propulsive motor activity in conscious mice. Fos immunoreactivity (IR), used as a marker of neuronal activation, was monitored in longitudinal muscle/myenteric plexus whole mount preparations of the distal colon 90 min after an intraperitoneal injection of 5-HTP. Double staining of Fos IR with peripheral choline acetyltransferase (pChAT) IR or NADPH-diaphorase activity was performed. The injection of 5-HTP (0.5, 1, 5, or 10 mg/kg ip) increased fecal pellet output and fluid content in a dose-related manner, with a peak response observed within the first 15 min postinjection. 5-HTP (0.5–10 mg/kg) dose dependently increased Fos expression in myenteric neurons, with a maximal response of 9.9 ± 1.0 cells/ganglion [ P < 0.05 vs. vehicle-treated mice (2.3 ± 0.6 cells/ganglion)]. There was a positive correlation between Fos expression and fecal output. Of Fos-positive ganglionic cells, 40 ± 4% were also pChAT positive and 21 ± 5% were NADPH-diaphorase positive in response to 5-HTP, respectively. 5-HTP-induced defecation and Fos expression were completely prevented by pretreatment with the selective 5-HT4 antagonist RS-39604. These results show that 5-HTP injected peripherally increases Fos expression in different populations of cholinergic and nitrergic myenteric neurons in the distal colon and stimulates propulsive colonic motor function through 5-HT4 receptors in conscious mice. These findings suggest an important role of activation of colonic myenteric neurons in the 5-HT4 receptor-mediated colonic propulsive motor response.

α-Synuclein Regulates Development and Function of Cholinergic Enteric Neurons in the Mouse Colon

Neuroscience ◽  
2019 ◽  
Vol 423 ◽  
pp. 76-85 ◽  
Author(s):  
M. Swaminathan ◽  
C. Fung ◽  
D.I. Finkelstein ◽  
J.C. Bornstein ◽  
J.P.P. Foong
Keyword(s):  
Enteric Neurons ◽  
Mouse Colon ◽  
And Function

Colonic migrating and nonmigrating motor complexes in dogs

1984 ◽  
Vol 246 (4) ◽  
pp. G355-G360 ◽  
Author(s):  
S. K. Sarna ◽  
R. Condon ◽  
V. Cowles
Keyword(s):  
Motor Activity ◽  
Terminal Ileum ◽  
Strain Gauges ◽  
Myoelectric Activity ◽  
Quiescent State ◽  
Bipolar Electrodes ◽  
Colonic Motor ◽  
Colonic Motor Activity ◽  
The Mean ◽  
Small Intestinal

We report here the characteristics of a cyclic motor activity in the colon of conscious dogs and its relationship to small intestinal migrating motor complexes (MMCs). The colonic motor activity was recorded by four equispaced strain gauges and small intestinal myoelectric activity by four equispaced bipolar electrodes. The colonic motor activity was characterized by rhythmic bursts of contractions. The mean durations of bursts of contractions varied from 7.0 to 11.5 min at the four colonic recording sites. Those bursts of contractions which migrated over at least three recording sites were called colonic migrating motor complexes (CMMCs). All other patterns of bursts of contractions were called colonic nonmigrating motor complexes (CNMCs). A total of 160 CMMCs were recorded during a total recording period of 132 h; 151 CMMCs migrated caudad and 9 orad. The mean period of caudad migrating CMMCs was 53.3 +/- 5.4 (SE) min, and their mean migration time was 11.3 +/- 1.2 (SE) min. The onset of CMMCs was not temporally related to the onset of small intestinal migrating myoelectric complexes in the duodenum or their arrival in the terminal ileum. CMMCs did not have phases I to IV like those of small intestinal MMCs, but two consecutive CMMCs were separated by a quiescent state or by one or more randomly occurring bursts of contractions (CNMCs).

scholarly journals Semaphorin 3A controls enteric neuron connectivity and is inversely associated with synapsin 1 expression in Hirschsprung disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jacques Gonzales ◽  
Catherine Le Berre-Scoul ◽  
Anne Dariel ◽  
Paul Bréhéret ◽  
Michel Neunlist ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Colonic Motility ◽  
Hirschsprung Disease ◽  
Perinatal Period ◽  
Cellular Level ◽  
Postnatal Period ◽  
Enteric Neurons ◽  
Semaphorin 3A ◽  
Potential Implication ◽  
Synapsin 1

Abstract Most of the gut functions are controlled by the enteric nervous system (ENS), a complex network of enteric neurons located throughout the wall of the gastrointestinal tract. The formation of ENS connectivity during the perinatal period critically underlies the establishment of gastrointestinal motility, but the factors involved in this maturation process remain poorly characterized. Here, we examined the role of Semaphorin 3A (Sema3A) on ENS maturation and its potential implication in Hirschsprung disease (HSCR), a developmental disorder of the ENS with impaired colonic motility. We found that Sema3A and its receptor Neuropilin 1 (NRP1) are expressed in the rat gut during the early postnatal period. At the cellular level, NRP1 is expressed by enteric neurons, where it is particularly enriched at growth areas of developing axons. Treatment of primary ENS cultures and gut explants with Sema3A restricts axon elongation and synapse formation. Comparison of the ganglionic colon of HSCR patients to the colon of patients with anorectal malformation shows reduced expression of the synaptic molecule synapsin 1 in HSCR, which is inversely correlated with Sema3A expression. Our study identifies Sema3A as a critical regulator of ENS connectivity and provides a link between altered ENS connectivity and HSCR.

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