Pathophysiologic Role of Neurotransmitters in Digestive Diseases

Yang, Xiaoxu; Lou, Jun; Shan, Weixi; Ding, Jianhong; Jin, Zhe; Hu, Yanxia; Du, Qian; Liao, Qiushi; Xie, Rui; Xu, Jingyu

doi:10.3389/fphys.2021.567650

Cited by 27 publications

(17 citation statements)

References 182 publications

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“…It requires a proper network of enteric neuronal and glial cells with balanced neurotransmission for GI physiological function regulation. 29,30 Chronic constipation is a multifactorial disorder with a complex pathogenesis that includes abnormalities within the ENS. 31,32 In terms of animal models, different approaches have been used to provide a better understanding of the pathophysiology of constipation where changes in density and/or altered morphology of the ENS, as well as altered neurotransmission, have been found.…”

Section: Discussionmentioning

confidence: 99%

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The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress

Lobo

Tramullas

Finger

et al. 2023

J Neurogastroenterol Motil

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Background/AimsChronic psychological stress affects gastrointestinal physiology which may underpin alterations in the immune response and epithelial transport, both functions are partly regulated by enteric nervous system. However, its effects on enteric neuroplasticity are still unclear. This study aims to investigate the effects of chronic unpredictable psychological stress on intestinal motility and prominent markers of enteric function. MethodsAdult male C57BL/6J mice were exposed to 19 day of unpredictable stress protocol schedule of social defeat and overcrowding. We investigated the effects on plasma corticosterone, food intake, and body weight. In vivo gastrointestinal motility was assessed by fecal pellet output and by whole-gastrointestinal transit (using the carmine red method). Tissue monoamine level, neural and glial markers, neurotrophic factors, monoamine signaling, and Toll-like receptor expression in the proximal and distal colon, and terminal ileum were also assessed. ResultsFollowing chronic unpredictable psychological stress, stressed mice showed increased food intake and body weight gain (P < 0.001), and reduced corticosterone levels (P < 0.05) compared to control mice. Stressed mice had reduced stool output without differences in water content, and showed a delayed gastrointestinal transit compared to control mice (P < 0.05). Stressed mice exhibited decreased mRNA expression of tyrosine hydroxylase (Th), brain-derived neurotrophic factor (Bdnf) and glial cell-derived neurotrophic factor (Gdnf), as well as Toll-like receptor 2 (Tlr2) compared to control (P < 0.05), only proximal colon. These molecular changes in proximal colon were associated with higher levels of monoamines in tissue. ConclusionUnpredictable psychological chronic stress induces region-specific impairment in monoamine levels and neuroplasticity markers that may relate to delayed intestinal transit.

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Section: Discussionmentioning

confidence: 99%

“…It requires a proper network of enteric neuronal and glial cells with balanced neurotransmission for GI physiological function regulation. 29 , 30 …”

Section: Discussionmentioning

confidence: 99%

The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress

Lobo

Tramullas

Finger

et al. 2023

J Neurogastroenterol Motil

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“…The release of serotonin (5-HT), a neurotransmitter monoamine related to the pathophysiological mechanisms of inflammatory disease in the gastrointestinal tract, increases inflammation in the context of intestinal inflammation, probably via the serotonin receptors 5-HTR1B and 5-HTR2A on DCs, increasing proinflammatory cytokines in activated B cells via NF-kB [ 89 , 90 ]. In contrast, the deletion, mainly in DCs, of 5-HTR, or even blockade with SB-269970, a 5-HTR antagonist, was shown to increase the severity of inflammation in colitis models, increasing the production of proinflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) [ 90 , 91 ], showing the possible close relationship between the neuronal mediators and the modulation of the immune system in the liver by DCs. Thus, these data suggest that the role of DCs via neuroendocrine-immune interactions may be related to the modulation of the immune response in the liver, but further studies are needed to clarify how this occurs.…”

Section: The Hepatic Tolerogenic Microenvironment and The Interplay W...mentioning

confidence: 99%

“…In addition, HSCs express the serotonin receptors 5-HT2A and 5-HT2B; these cells also take up and release serotonin through the 5-HT receptor [ 98 ]. These receptors contribute to hepatic fibrosis, HSC proliferation, gene transcription, and apoptosis [ 90 , 99 ]. Human HSCs also respond to NE, as cellular exposure to this neurotransmitter triggers pro-inflammatory responses with the secretion of inflammatory chemokines, such as RANTES and IL-8, and calcium spikes, which were partially attenuated with the administration of a nonspecific beta-blocker (propranolol) [ 100 ].…”

Section: The Hepatic Tolerogenic Microenvironment and The Interplay W...mentioning

confidence: 99%

Immunological Tolerance in Liver Transplant Recipients: Putative Involvement of Neuroendocrine-Immune Interactions

Gama

Cardoso

Bisaggio

et al. 2022

Cells

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The transplantation world changed significantly following the introduction of immunosuppressants, with millions of people saved. Several physicians have noted that liver recipients that do not take their medication for different reasons became tolerant regarding kidney, heart, and lung transplantations at higher frequencies. Most studies have attempted to explain this phenomenon through unique immunological mechanisms and the fact that the hepatic environment is continuously exposed to high levels of pathogen-associated molecular patterns (PAMPs) or non-pathogenic microorganism-associated molecular patterns (MAMPs) from commensal flora. These components are highly inflammatory in the periphery but tolerated in the liver as part of the normal components that arrive via the hepatic portal vein. These immunological mechanisms are discussed herein based on current evidence, although we hypothesize the participation of neuroendocrine-immune pathways, which have played a relevant role in autoimmune diseases. Cells found in the liver present receptors for several cytokines, hormones, peptides, and neurotransmitters that would allow for system crosstalk. Furthermore, the liver is innervated by the autonomic system and may, thus, be influenced by the parasympathetic and sympathetic systems. This review therefore seeks to discuss classical immunological hepatic tolerance mechanisms and hypothesizes the possible participation of the neuroendocrine-immune system based on the current literature.

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“…In the brain, 5-HT helps regulate behaviors such as sleep and learning [ 1 , 2 ] as well as onset of anxiety and depression [ 3 ]. 5-HT is produced at even higher levels in the mammalian GI tract in pathways responsible for peristalsis [ 4 ], visceral sensation [ 5 ], and symptoms such as nausea [ 6 ], and has been implicated in a number of functional GI disorders [ 7 , 8 , 9 , 10 ]. Often, the goal is to quantify 5-HT concentrations within tissues or bodily fluids and correlate this with biological processes, especially underlying disease.…”

Section: Introductionmentioning

confidence: 99%

Adsorption Kinetic Model Predicts and Improves Reliability of Electrochemical Serotonin Detection

Chapin

Han

Ghodssi

2023

MPs

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Serotonin (5-HT) is a neurotransmitter involved in many biophysiological processes in the brain and in the gastrointestinal tract. Electrochemical methods are commonly used to quantify 5-HT, but their reliability may suffer due to the time-dependent nature of adsorption-limited 5-HT detection, as well as electrode fouling over repeated measurements. Mathematical characterization and modeling of adsorption-based electrochemical signal generation would improve reliability of 5-HT measurement. Here, a model was developed to track 5-HT electrode adsorption and resulting current output by combining Langmuir adsorption kinetic equations and adsorption-limited electrochemical equations. 5-HT adsorption binding parameters were experimentally determined at a carbon-nanotube coated Au electrode: KD = 7 × 10−7 M, kon = 130 M−1 s−1, koff = 9.1 × 10−5 s−1. A computational model of 5-HT adsorption was then constructed, which could effectively predict 5-HT fouling over 50 measurements (R2 = 0.9947), as well as predict electrode responses over varying concentrations and measurement times. The model aided in optimizing the measurement of 5-HT secreted from a model enterochromaffin cell line—RIN14B—minimizing measurement time. The presented model simplified and improved the characterization of 5-HT detection at the selected electrode. This could be applied to many other adsorption-limited electrochemical analytes and electrode types, contributing to the improvement of application-specific modeling and optimization processes.

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Pathophysiologic Role of Neurotransmitters in Digestive Diseases

Cited by 27 publications

References 182 publications

The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress

The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress

Immunological Tolerance in Liver Transplant Recipients: Putative Involvement of Neuroendocrine-Immune Interactions

Adsorption Kinetic Model Predicts and Improves Reliability of Electrochemical Serotonin Detection

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