Imipramine improves visceral sensation and gut barrier in rat models of irritable bowel syndrome

Nozu, Tsukasa; Miyagishi, Saori; Ishioh, Masatomo; Takakusaki, Kaoru; Okumura, Toshikatsu

doi:10.1016/j.ejphar.2020.173565

Cited by 11 publications

(5 citation statements)

References 46 publications

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“…Losartan can prevent visceral pain and colonic hyperpermeability in IBS rats, which may be dependent on the PPAR- γ, AMPK, and central dopamine D 2 pathways, or mediated by opioids and nitric oxide ( 26 ). Imipramine may also inhibit visceral hypersensitivity and colonic permeability in an IBS animal model through the α-2-adrenoceptor, dopamine D 2, and opioid pathways, and improve the intestinal barrier ( 37 ).…”

Section: Neurotransmittersmentioning

confidence: 99%

Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome

et al. 2022

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Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder of unknown etiology. IBS is caused by a disruption in the gut-brain axis. Given the importance of the gut microbiota in maintaining local and systemic homeostasis of immunity, endocrine, and other physiological processes, the microbiota-gut-brain axis has been proposed as a key regulator in IBS. Neurotransmitters have been shown to affect blood flow regulation, intestinal motility, nutrient absorption, the gastrointestinal immune system, and the microbiota in recent studies. It has the potential role to play a function in the pathophysiology of the gastrointestinal and neurological systems. Transmitters and their receptors, including 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, and histamine, play an important role in IBS, especially in visceral sensitivity and gastrointestinal motility. Studies in this field have shed light on revealing the mechanism by which neurotransmitters act in the pathogenesis of IBS and discovering new therapeutic strategies based on traditional pharmacological approaches that target the nervous system or novel therapies that target the microbiota.

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Section: Neurotransmittersmentioning

confidence: 99%

Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome

et al. 2022

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“…Male mice were selected as the preferred experimental subjects due to the obvious fluctuations in hormone levels observed in female mice, which could potentially introduce confounding factors into the results. Previous studies have predominantly utilized male mouse models for investigating IBS [36‒38]. Our results showed that the chemical genetic activation of the MCH neurons in the LHA resulted in anxiety- and depressive-like behaviors and heightened intestinal motility and visceral sensitivity.…”

Section: Discussionmentioning

confidence: 66%

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea

Ming,

Gao,

Sun

et al. 2024

Neuroendocrinology

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Introduction: Irritable bowel syndrome with diarrhea (IBS-D) is frequently accompanied by depression and anxiety, resulting in a reduced quality of life and increased medical expenditures. Although psychological factors are known to play an important role in the genesis and development of IBS-D, an understanding of the central neural control of intestinal dysfunction remains elusive. Melanin-concentrating hormone (MCH) is a gut-brain peptide involved in regulating feeding, sleep-wake rhythms, and emotional states. Methods: This study investigated the regulation of the MCHergic neural circuit from the lateral hypothalamic area (LHA) to the dorsal raphe nucleus (DRN) on anxiety- and depression-like behaviors, intestinal motility, and visceral hypersensitivity in a mice model of IBS-D. The models of IBS-D were prepared by inducing chronic unpredictable mild stress. Results: Chemogenetic activation of the MCH neurons in the LHA could excite serotonin (5-HT) neurons in the DRN and induce anxiety- and depression-like behaviors and IBS-D-like symptoms, which could be recovered by microinjection of the MCH receptor antagonist SNAP94847 into the DRN. The mice model of IBS-D showed a reduction of 5-HT and brain-derived neurotrophic factor (BDNF) expression in the DRN, while an elevation of 5-HT and BDNF was observed in the colon through immunofluorescent staining, ELISA, and Western blot analysis. SNAP94847 treatment in the DRN alleviated anxiety- and depression-like behaviors, improved intestinal motility, and alleviated visceral hypersensitivity responses by normalizing the 5-HT and BDNF expression in the DRN and colon. Conclusion: This study suggests that the activation of MCH neurons in the LHA may induce IBS-D symptoms via the DRN and that the MCH receptor antagonist could potentially have therapeutic effects.

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“…Brucella abortus, on the other hand, may induce depression after inducing inflammatory colitis [31] following the disruption of colorectal mucosae linings [32,33], colorectal serotonin availability [34,35] and dysbiosis [9,36]. Imipramine administration may reverse this condition by improving gut's visceral sensation, serotonin local availability and gut barrier [37]. Body condition, on the other hand, could have been improved in ImBa mice following the drop on IL-6, since elevations of this cytokine sensitizes pain pathways and produces hyperalgesia through various mechanisms [38,39].…”

Section: Discussionmentioning

confidence: 99%

A Short Oro-Gastric Imipramine Administration in Brucella abortus 2308 Infected Mice Decreases CFU Count at the Spleen; Improves the IFN-γ/IL-6 Ratio; Restores Serotonin Levels in the Hippocampus, Muscular Strength, and Mood

Maldonado-Tapia¹,

Maldonado-García²,

Pérez‐Sánchez³

et al. 2022

Preprint

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Brucellosis infection induces fever, chills, sweats, headache, myalgia, arthralgia, anorexia, fa-tigue, and mood disorders. In mice, it causes a rise in IL-6, TNF-, and IFN-; and reduces sero-tonin and dopamine levels in hippocampus. There is loss in muscle strength and equilibrium and increased anxiety and hopelessness. Imipramine (ImiP) is a tricyclic antidepressant that increases the capacity of macrophages to destroy intracellular microorganisms in vivo. The effect of ImiP was evaluated in Balb/c mice infected with Brucella abortus 2308. Serum levels were determined in IFN-, IL-6, TNF-, IL-12, MCP-1, and IL-10 by FACS; the bacterial count in the spleen, by CFU; the serotonin concentration in the hippocampus, by HPLC; and strength, equilibrium, and mood by behavioral tests. Our results showed that infected vs. control mice had a significant rise in lev-els of IFN-, IL-6, TNF-, and IL-12 with a low IFN-/IL-6 ratio, elevated bacterial-counts, alter-ations in serotonin concentration at hippocampus, and decreased muscular strength, equilibrium, and mood. Infected mice treated with ImiP vs. infected mice showed: 1) improved mood; 2) in-creased hippocampal serotonin availability, splenic dendritic cells, and macrophage phagocytic activity; and 3) upturn inflammation and reduced CFU ability. Our results support that ImiP fa-vors positive outcomes in subjects handling Brucella infections likely by improving psychoim-mune resilience.

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Imipramine improves visceral sensation and gut barrier in rat models of irritable bowel syndrome

Cited by 11 publications

References 46 publications

Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome

Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome

Regulation of the MCHergic Neural Circuit to Dorsal Raphe Nucleus on Emotion-Related Behaviors and Intestinal Dysfunction in Mice Model of Irritable Bowel Syndrome with Diarrhea

A Short Oro-Gastric Imipramine Administration in <em>Brucella abortus</em> 2308 Infected Mice Decreases CFU Count at the Spleen; Improves the IFN-γ/IL-6 Ratio; Restores Serotonin Levels in the Hippocampus, Muscular Strength, and Mood

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