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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 4741

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Dr. Takahiko Shiina

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Laboratory of Veterinary Physiology, Department of Joint Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
Interests: nervous system and gastrointestinal diseases

Special Issue Information

Dear Colleagues,

Motility of gastrointestinal tracts, such as the esophagus, stomach, small and large intestines, is regulated by the central nervous system and the enteric nervous system. The peristaltic movement is induced by the activation of intrinsic sensory neurons, which are coupled via modulatory interneurons to excitatory and inhibitory motor neurons projecting into the smooth muscle layer. The central nervous system is also involved in gastrointestinal motor regulation. For example, esophageal motility is controlled by the vago-vagal reflex, and the supraspinal defecation center in the brain stem accelerates or suppresses the spinal defecation center, which controls the enteric nervous system in the colorectum. Impairment of the interactions between nervous system and gastrointestinal motility is closely related to the development of gastrointestinal disorders such as the irritable bowel syndrome (IBS).

We cordially invite researchers to submit original or review papers addressing the morphology, physiology, pathophysiology, pharmacology, biochemistry, and molecular biology of the interactions between the nervous system and gastrointestinal motility.

Dr. Takahiko Shiina
Guest Editor

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Keywords

gastrointestinal tracts
central nervous system
enteric nervous system
motor regulation
peristalsis
vomiting
gastrointestinal disorder
smooth muscle
striated muscle
sphincter
esophagus
stomach
duodenum
jejunum
ileum
cecum
colon
rectum
rumen

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Research

20 pages, 5412 KiB

Open AccessArticle

Unveiling the Mystery of the Stimulatory Effects of Arecoline: Its Relevance to the Regulation of Neurotransmitters and the Microecosystem in Multi-Ecological Intestinal Sites

by Junxi Shen, Mengsi Zhou, Nenqun Xiao, Zhoujin Tan and Xuejuan Liang

Int. J. Mol. Sci. 2025, 26(7), 3150; https://doi.org/10.3390/ijms26073150 - 28 Mar 2025

Viewed by 281

Abstract

The dried ripe seeds and pericarp of Areca catechu L., a palm species, possess significant economic value. Masticating betel nut is also a long-standing and widely prevalent lifestyle habit rooted in history, known for its stimulating effect. This effect stems primarily from arecoline, the principal active compound in betel nut. This study investigates the potential mechanisms underlying the stimulating effects of arecoline, focusing on neurotransmitters, neurotrophic factors, and the microecosystem in multi-ecological intestinal sites. After arecoline intervention in mice, significant changes were observed in locomotor activity. The levels of dopamine (DA) in liver tissue and 5-hydroxytryptamine (5-HT) in brain tissue were significantly reduced. There was a significant increase in microbial activity in the feces and in the level of n-valeric acid in the intestinal content. At the genus level, the relative abundance of Clostridium was significantly reduced, whereas the relative abundances of Helicobacter and Aquincola were markedly increased. Helicobacter, Aquincola, Faecalibaculum, and Liquorilactobacillus were signature genera in the arecoline-treated group. The 5-HT level was significantly negatively correlated with the abundance of the signature genera Aquincola, Helicobacter, and Liquorilactobacillus in the arecoline group. The ingestion of arecoline can alter the behavioral patterns of mice, causing significant changes in the 5-HT levels in brain tissue and exerting regulatory effects on the microecosystem in multi-ecological intestinal sites. These findings will provide a reference for the future development and utilization of betel nut. Full article

(This article belongs to the Special Issue Interactions between the Nervous System and Gastrointestinal Motility)

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20 pages, 13199 KiB

Open AccessArticle

Peripherally Restricted Activation of Opioid Receptors Influences Anxiety-Related Behaviour and Alters Brain Gene Expression in a Sex-Specific Manner

by Nabil Parkar, Wayne Young, Trent Olson, Charlotte Hurst, Patrick Janssen, Nick J. Spencer, Warren C. McNabb and Julie E. Dalziel

Int. J. Mol. Sci. 2024, 25(23), 13183; https://doi.org/10.3390/ijms252313183 - 7 Dec 2024

Viewed by 1380

Abstract

Although effects of stress-induced anxiety on the gastrointestinal tract and enteric nervous system (ENS) are well studied, how ENS dysfunction impacts behaviour is not well understood. We investigated whether ENS modulation alters anxiety-related behaviour in rats. We used loperamide, a potent μ-opioid receptor agonist that does not cross the blood–brain barrier, to manipulate ENS function and assess changes in behaviour, gut and brain gene expression, and microbiota profile. Sprague Dawley (male/female) rats were acutely dosed with loperamide (subcutaneous) or control solution, and their behavioural phenotype was examined using open field and elevated plus maze tests. Gene expression in the proximal colon, prefrontal cortex, hippocampus, and amygdala was assessed by RNA-seq and caecal microbiota composition determined by shotgun metagenome sequencing. In female rats, loperamide treatment decreased distance moved and frequency of supported rearing, indicating decreased exploratory behaviour and increased anxiety, which was associated with altered hippocampal gene expression. Loperamide altered proximal colon gene expression and microbiome composition in both male and female rats. Our results demonstrate the importance of the ENS for communication between gut and brain for normo-anxious states in female rats and implicate corticotropin-releasing hormone and gamma-aminobutyric acid gene signalling pathways in the hippocampus. This study also sheds light on sexually dimorphic communication between the gut and the brain. Microbiome and colonic gene expression changes likely reflect localised effects of loperamide related to gut dysmotility. These results suggest possible ENS pharmacological targets to alter gut to brain signalling for modulating mood. Full article

(This article belongs to the Special Issue Interactions between the Nervous System and Gastrointestinal Motility)

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15 pages, 4612 KiB

Open AccessArticle

Clinicopathological Appearance of Epidermal Growth-Factor-Containing Fibulin-like Extracellular Matrix Protein 1 Deposition in the Lower Gastrointestinal Tract: An Autopsy-Based Study

by Shojiro Ichimata, Yukiko Hata, Koji Yoshida and Naoki Nishida

Int. J. Mol. Sci. 2024, 25(14), 7581; https://doi.org/10.3390/ijms25147581 - 10 Jul 2024

Viewed by 1177

Abstract

This study examined the patterns of epidermal growth-factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) deposition in the small intestine and colon to evaluate the association between the histopathological severity of EFEMP1 deposition and constipation and determine the colocalization of amyloid transthyretin (ATTR) and EFEMP1 deposits. In 40 older cases (≥80 years of age), EFEMP1 deposition in the small intestine initiated in the submucosal and subserous vessels, subserous interstitium, and serosa (early stage), progressing to the muscularis propria and peri-Auerbach plexus area (intermediate stage), and finally spreading diffusely to other areas, excluding the mucosa and muscularis mucosa (advanced stage). The colon had a similar pattern of progression. During the middle-to-advanced stages, amyloid formation was observed in some vascular and serous deposits. A subgroup of cases was identified in which EFEMP1 deposition was the only presumed cause of constipation. Additionally, we demonstrated the colocalization of ATTR and EFEMP1 deposition. Apple-green birefringence was detected under polarized light only in approximately one-half of the cases in the small intestine and one-third of the cases in the colon. These findings strongly suggest that EFEMP1 deposits are correlated with pathological conditions of the lower gastrointestinal tract. As the histopathological diagnosis using Congo red-stained specimens is challenging, the combined use of elastic fiber staining and EFEMP1 immunohistochemistry is recommended to identify EFEMP1 deposition. Full article

(This article belongs to the Special Issue Interactions between the Nervous System and Gastrointestinal Motility)

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14 pages, 6730 KiB

Open AccessArticle

Accelerated Electron Ionization-Induced Changes in the Myenteric Plexus of the Rat Stomach

by Raina Ardasheva, Veselin Popov, Viktor Yotov, Natalia Prissadova, Mina Pencheva, Iva Slavova, Valentin Turiyski and Athanas Krastev

Int. J. Mol. Sci. 2024, 25(12), 6807; https://doi.org/10.3390/ijms25126807 - 20 Jun 2024

Cited by 1 | Viewed by 1114

Abstract

The influence of accelerated electrons on neuronal structures is scarcely explored compared to gamma and X-rays. This study aims to investigate the effects of accelerated electron radiation on some pivotal neurotransmitter circuits (cholinergic and serotonergic) of rats’ myenteric plexus. Male Wistar rats were irradiated with an electron beam (9 MeV, 5 Gy) generated by a multimodality linear accelerator. The contractile activity of isolated smooth muscle samples from the gastric corpus was measured. Furthermore, an electrical stimulation (200 μs, 20 Hz, 50 s, 60 V) was performed on the samples and an assessment of the cholinergic and serotonergic circuits was made. Five days after irradiation, the recorded mechanical responses were biphasic—contraction/relaxation in controls and contraction/contraction in irradiated samples. The nature of the contractile phase of control samples was cholinergic with serotonin involvement. The relaxation phase involved ACh-induced nitric oxide release from gastric neurons. There was a significant increase in serotonergic involvement during the first and second contractile phases of the irradiated samples, along with a diminished role of acetylcholine in the first phase. This study demonstrates an increased involvement of serotonergic neurotransmitter circuits in the gastric myenteric plexus caused by radiation with accelerated electrons. Full article

(This article belongs to the Special Issue Interactions between the Nervous System and Gastrointestinal Motility)

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