Article
Biochemical Research Methods
Alex Gonzalez-Vergara, Benjamin Benavides, Marcela Julio-Pieper
Summary: Neuropeptides are diverse signaling molecules found in the central and peripheral nervous systems, including the enteric nervous system. Studying their role in diseases and therapeutic potential requires addressing analytical challenges, particularly in the low abundance of neuropeptides in the ENS tissue. This review discusses these challenges and opportunities for technical development.
JOURNAL OF NEUROSCIENCE METHODS
(2023)
Review
Physiology
Keith A. Sharkey, Gary M. Mawe
Summary: The gastrointestinal tract is the most complex organ system in the body, controlling digestion and defense functions through the enteric nervous system. This system interacts with the immune system, gut microbiota, and epithelium to maintain mucosal defense and barrier function. Recent developments have improved our understanding of the molecular architecture, function, and regulation of the enteric nervous system, highlighting its importance in maintaining intestinal homeostasis.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Biochemical Research Methods
Zitong Huang, Lu Liao, Zhesheng Wang, Yulin Lu, Weiming Yan, Hongying Cao, Bo Tan
Summary: This study presents a simple and rapid method for preparing whole mounts of rat colon, facilitating the easy separation of LMMPs and allowing clear visualization of structures through immunofluorescence staining. Compared to existing methods, this approach is more efficient and provides sufficient high-quality LMMPs in a quicker manner.
JOURNAL OF NEUROSCIENCE METHODS
(2021)
Article
Gastroenterology & Hepatology
Wai Ping Yew, Adam Humenick, Bao Nan Chen, David A. Wattchow, Marcello Costa, Phil G. Dinning, Simon J. H. Brookes
Summary: Ex vivo intracellular recordings and dye fills, combined with immunohistochemistry, are used to analyze the enteric nervous system of laboratory animals. Treatment with a collagenase/neutral protease mix improves recording success and reduces damage. Most dye-filled myenteric neurons are uni-axonal, and there is a low correlation between morphology and electrophysiology. Neurons immunoreactive for nitric oxide synthase are more excitable and distinctive grooves on the neuron surface may represent preferential sites of synaptic inputs.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Article
Neurosciences
Jean-Baptiste Cavin, Preedajit Wongkrasant, Joel B. Glover, Onesmo B. Balemba, Wallace K. MacNaughton, Keith A. Sharkey
Summary: The enteric nervous system regulates the functions of the gastrointestinal tract, and its response to changes in the gut lumen is not well understood. This study used live-cell confocal recordings to investigate neuronal response to luminal mechanical and chemical stimuli. The results show that intestinal distension regulates the excitability of enteric neural circuits via mechanosensitive channels, and the content of the intestinal lumen dynamically regulates the excitability of enteric neural circuits.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Gastroenterology & Hepatology
Timothy J. Hibberd, Marcello Costa, David J. Smolilo, Lauren J. Keightley, Simon J. Brookes, Phil G. Dinning, Nick J. Spencer
Summary: Colonic motor complexes (CMCs) are the main neurogenic activity that initiates propulsion in the guinea pig distal colon. In this study, it was found that CMCs, evoked by an intraluminal pellet, could be restored during nicotinic receptor blockade by pharmacological agents that directly or indirectly enhance the excitability of intrinsic primary afferent neurons (IPANs). IPANs are the only enteric neurons in the colon that contain calcitonin gene-related peptide (CGRP). Blocking CGRP receptors decreased the frequency of CMCs, implicating their role in CMC initiation. These results support the involvement of IPANs in the initiation of CMCs.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Microbiology
Fernando A. Vicentini, Catherine M. Keenan, Laurie E. Wallace, Crystal Woods, Jean-Baptiste Cavin, Amanda R. Flockton, Wendy B. Macklin, Jaime Belkind-Gerson, Simon A. Hirota, Keith A. Sharkey
Summary: The study demonstrates the role of the gut microbiota in regulating the structure and function of the GI tract in a sex-independent manner. The microbiota is essential for maintaining ENS integrity by regulating enteric neuronal survival and promoting neurogenesis. Molecular determinants such as LPS and SCFA play a key role in regulating enteric neuronal survival and neurogenesis.
Article
Biochemistry & Molecular Biology
Yun Ju Choi, Hee Jin Song, Ji Eun Kim, Su Jin Lee, You Jeong Jin, Yu Jeong Roh, Ayun Seol, Hye Sung Kim, Dae Youn Hwang
Summary: The study found that C3 deficiency in mice led to prominent constipation phenotypes in the mid colon, including decreased stool parameters, changes in histological structure, and suppressed mucin secretion. These results suggest that dysregulation of the enteric nervous system (ENS) may play an important role in C3 deficiency-induced constipation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Sarah A. Najjar, Brian S. Edwards, Kathryn M. Albers, Brian M. Davis, Kristen M. Smith-Edwards
Summary: This study demonstrates that colon epithelial cells likely use purinergic and serotonergic signaling to initiate activity in myenteric neurons, leading to local contractions and facilitating large-scale coordination of ENS activity responsible for whole colon motility patterns.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ines Hecking, Lennart Norman Stegemann, Verena Theis, Matthias Vorgerd, Veronika Matschke, Sarah Stahlke, Carsten Theiss
Summary: Research has found that the enteric nervous system (ENS), through its connection to the microbiome and the immune system, may play a role in the pathological changes seen in neurodegenerative diseases. Vascular endothelial growth factor (VEGF) has shown neuroprotective effects in both the central and peripheral nervous systems, and can directly protect enteric neurons in the ENS. These findings suggest a promising approach for neuroprotection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Marcello Costa, Lauren J. Keightley, Timothy J. Hibberd, Lukasz Wiklendt, David J. Smolilo, Phil G. Dinning, Simon J. Brookes, Nick J. Spencer
Summary: Two distinct types of colonic motor complexes (CMCs) were identified in isolated mouse colon, complete and incomplete CMCs, with differences in the duration of smooth muscle action potentials, propagation speed, and frequency. Recognizing these different patterns of motility will be important for future interpretation of murine colonic motility recordings. Alternating patterns of motor activity in the proximal colon, but not in the distal colon, may reflect specific neural mechanisms for fecal pellet formation.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Review
Biochemistry & Molecular Biology
Laura Lopez-Pingarron, Henrique Almeida, Marisol Soria-Aznar, Marcos C. Reyes-Gonzales, Ana B. Rodriguez-Moratinos, Antonio Munoz-Hoyos, Joaquin J. Garcia
Summary: The enteric nervous system (ENS) consists of two plexuses, submucosal and myenteric, which regulate gastrointestinal motility through communication with interstitial cells of Cajal (ICCs). ICCs generate slow waves that control smooth muscle contraction and are involved in enteric neurotransmission. Oxidative stress and neurological diseases can disrupt the interaction between ICCs, the ENS, and the central nervous system (CNS), leading to gastrointestinal motility disorders. This review discusses disturbances in enteric neurotransmission and ICC function that contribute to abnormal gut motility.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Veterinary Sciences
Roberto Chiocchetti, Giorgia Galiazzo, Fiorella Giancola, Claudio Tagliavia, Chiara Bernardini, Monica Forni, Marco Pietra
Summary: The distribution of serotonin transporter immunoreactivity in the dog intestine is similar to that in rats and humans, suggesting a conserved role in serotonin reuptake mechanism.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Gastroenterology & Hepatology
Hiroyuki Nakamori, Kenta Noda, Retsu Mitsui, Hikaru Hashitani
Summary: The roles of enteric dopaminergic neurons in the generation of colonic peristalsis were investigated by studying the effects of various neurotransmitter blockers on peristaltic waves in rat colonic segments. Dopaminergic neurons appeared to facilitate nitrergic neurons via D-1-like receptors to stabilize asynchronous contractile activity resulting in the generation of colonic peristalsis.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Neurosciences
Jing Feng, Tim J. Hibberd, Jialie Luo, Pu Yang, Zili Xie, Lee Travis, Nick J. Spencer, Hongzhen Hu
Summary: Through chemogenetic strategy, reduction of CAL neurons in the colon led to decreased colonic length and pellet sizes without overt inflammation. Interestingly, there was an increase in frequency and decrease in size of colonic motor complexes (CMCs) with lack of preferential anterograde migration. This suggests that calretinin neurons may play a role in pacing, force, and polarity of CMCs in the large bowel.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Timothy J. Hibberd, Wai Ping Yew, Kelsi N. Dodds, Zili Xie, Lee Travis, Simon J. Brookes, Marcello Costa, Hongzhen Hu, Nick J. Spencer
Summary: This study comprehensively quantified CGRP+ myenteric neurons in mouse colon, which aligns with the expected range of an intrinsic primary afferent neuron (IPAN) marker.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Gastroenterology & Hepatology
Paul T. Heitmann, Lauren Keightley, Lukasz Wiklendt, David A. Wattchow, Simon S. J. Brookes, Nicholas J. Spencer, Marcello Costa, Phil G. Dinning
Summary: This study aimed to describe the effects of loperamide on neuromuscular function in the human colon. The findings suggest that loperamide primarily alters colonic function by acting on inhibitory motor neurons or alternative non-opioid receptor pathways.
NEUROGASTROENTEROLOGY AND MOTILITY
(2022)
Article
Neurosciences
Kelsi N. Dodds, Melinda A. Kyloh, Lee Travis, Mack Cox, Tim J. Hibberd, Nick J. Spencer
Summary: This study investigated the distribution of thoracolumbar and lumbosacral spinal afferent neurons in the mouse uterine horn. The results showed that lumbosacral spinal afferent nerves provide relatively modest sensory innervation across the mouse uterine horn, with no regional specificity, compared to thoracolumbar spinal afferents.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biology
Melinda A. Kyloh, Timothy J. Hibberd, Joel Castro, Andrea M. Harrington, Lee Travis, Kelsi N. Dodds, Lukasz Wiklendt, Stuart M. Brierley, Vladimir P. Zagorodnyuk, Nick J. Spencer
Summary: This study developed a surgical method to selectively remove specific dorsal root ganglia (DRG) in mice, providing insights into the contribution of thoracolumbar and lumbosacral DRG to pain signaling and behavior. The technique allowed researchers to investigate sensory pathway functions in conscious, free-moving animals without genetic modification.
COMMUNICATIONS BIOLOGY
(2022)
Article
Neurosciences
Zili Xie, Jing Feng, Timothy J. Hibberd, Bao Nan Chen, Yonghui Zhao, Kaikai Zang, Xueming Hu, Xingliang Yang, Lvyi Chen, Simon J. Brookes, Nick J. Spencer, Hongzhen Hu
Summary: By ablating the sensory channels TRPV1 and Piezo2 from colon-innervating neurons, the visceromotor responses (VMR) induced by colorectal distention (CRD) are significantly reduced in mice. Selective ablation of Piezo2 channels in TRPV1 lineage neurons reduces mechanically evoked visceral afferent action potential firing and CRD-induced VMR under physiological conditions, as well as in mouse models of zymosan-induced IBS and partial colon obstruction (PCO). These findings demonstrate the important role of the mechanosensitive Piezo2 channels in TRPV1-lineage neurons in visceral mechanosensitivity and nociception under physiological conditions, as well as in visceral hypersensitivity under pathological conditions.
Article
Neurosciences
Nick J. Spencer, Tim Hibberd, Zili Xie, Hongzhen Hu
Summary: In recent years, there has been increasing interest in understanding the communication between the gut and the brain. New data suggests that the sensory nerve pathways between the two may have a more significant impact on health and disease than previously assumed. While sensory nerve endings in the skin have been extensively studied, there is a lack of knowledge about most types of visceral afferents, especially those that innervate abdominal organs like the gut. Recent studies have identified nerve endings of spinal afferents in visceral organs, emphasizing their role in pain perception from the gut to the brain. Surprisingly, the majority of these spinal afferent nerve endings in the gut express the TRPV1 ion channel, commonly associated with nociceptive neurons. Furthermore, these nerve endings are activated at low thresholds within the normal physiological range, suggesting a complex nature of visceral nociception. This highlights the need to redefine nociceptors in the gut, which may involve multiple morphological types of spinal afferent nerve endings.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Physiology
David J. J. Smolilo, Timothy J. J. Hibberd, Marcello Costa, Phil G. G. Dinning, Lauren J. J. Keightley, Dayan De Fontgalland, David A. Wattchow, Nick J. J. Spencer
Summary: The speed of pellet propulsion in the isolated guinea pig distal colon in vitro is higher than in vivo measurements, suggesting inhibitory mechanisms from outside the gut. The study aimed to investigate the effects of sympathetic nerve stimulation on different motor behaviors of the distal colon. Results showed that electrical stimulation of colonic nerves inhibited transient neural events (TNEs) and pellet propulsion, while significant inhibition of colonic motor complexes (CMCs) required higher frequencies of stimulation. The findings suggest differential sensitivities to sympathetic input among distinct neurogenic motor behaviors of the colon and raise the possibility of paradoxical effects of CMCs on pellet movement suppression in vivo.
PHYSIOLOGICAL REPORTS
(2023)
Article
Pharmacology & Pharmacy
Stewart Ramsay, Nick J. Spencer, Vladimir Zagorodnyuk
Summary: The aim of this study is to determine the role of endocannabinoids, anandamide (AEA) and 2-arachidonolylglycerol (2-AG), in regulating mechanosensitivity of probable nociceptive neurons innervating the bladder - capsaicin-sensitive mucosal afferents. The results showed that AEA potentiated the mechanical response of mucosal afferents, while 2-AG inhibited their response. These findings have important implications for understanding the role of endocannabinoids in regulating bladder sensation and function.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Nabil Parkar, Julie E. Dalziel, Nick J. Spencer, Patrick Janssen, Warren C. McNabb, Wayne Young
Summary: Gastrointestinal (GI) motility relies on the enteric nervous system (ENS) and is crucial for digestion. Dysfunction in the ENS can lead to constipation. Animal models have been developed to mimic constipation symptoms through pharmacological manipulations, and studies have shown an association between altered GI motility and gut microbial population. However, little is known about the changes in gut microbiota resulting from slowed GI motility induced by medication, and the current understanding is based on studies using faecal samples which do not accurately represent the intestinal microbiome. This study aimed to investigate how delayed GI transit, caused by opioid receptor agonism in the ENS, affects caecal microbiota composition, and the results showed significant differences in microbial composition between treatment groups, with Bacteroides being relatively abundant in the group with slowed GI transit.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Bao Nan Chen, Adam Humenick, Wai Ping Yew, Lukasz Wiklendt, Phil G. Dinning, Nick J. Spencer, David A. Wattchow, Marcello Costa, Simon J. H. Brookes
Summary: This study used multiplexed immunohistochemistry to classify myenteric neurons of human colon into 20 classes. Cell morphology, soma size, and associations with axon terminals were quantified, providing a comprehensive understanding of the human myenteric plexus.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Physiology
Timothy J. Hibberd, Stewart Ramsay, Phaedra Spencer-Merris, Phil G. Dinning, Vladimir P. Zagorodnyuk, Nick J. Spencer
Summary: This review discusses the role of peripheral clocks in regulating major colonic functions, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. It also describes the interactions between pathophysiological states such as irritable bowel syndrome and ulcerative colitis and circadian rhythmicity.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Surgery
David A. Wattchow, Simon J. Brookes, Nick J. Spencer, Paul T. Heitmann, Roberto De Giorgio, Marcello Costa, Phil. G. Dinning
Summary: Motor function of the colon is crucial for health, and our understanding of its mechanisms is based on various experimental techniques. This article synthesizes key findings from these approaches to help surgeons better manage colonic conditions.
ANZ JOURNAL OF SURGERY
(2023)
Proceedings Paper
Gastroenterology & Hepatology
Nick J. Spencer, Marcello Costa
Summary: The enteric nervous system (ENS) plays a crucial role in the cyclical motor activity of the gastrointestinal tract, but the activation of the thousands of neurons within the ENS that generate neurogenic contractions has remained a mystery. Neuronal imaging studies on the mouse large intestine have provided insights into how different classes of myenteric neurons are activated during cyclical motor patterns, and it has been found that large populations of myenteric neurons coordinate their firing across interconnected ganglia, regardless of their functional class. The polarity of the enteric circuits and the rhythmic activity of specific classes of enteric neurons at approximately 2 Hz are important factors in the propulsion of content along the mouse colon. The mechanisms that initiate and terminate the patterned firing of enteric neurons during cyclic activity remain to be determined, presenting an exciting challenge for future studies.
ENTERIC NERVOUS SYSTEM II
(2022)
Proceedings Paper
Gastroenterology & Hepatology
Bradley B. Barth, Nick J. Spencer, Warren M. Grill
Summary: The motor patterns of the colon are coordinated by the enteric nervous system (ENS) and involve various cell types. Recent advances in research have revealed the complexity of the circuitry underlying colonic motor patterns. The colonic motor complex (CMC) is described as a robust control system, and electrical stimulation can disrupt its coordination and propagation.
ENTERIC NERVOUS SYSTEM II
(2022)
Proceedings Paper
Gastroenterology & Hepatology
Simon Brookes, Nan Chen, Adam Humenick, Marcello Costa, Phil Dinning, Paul Heitmann, Dominic Parker, David Smolilo, Nick J. Spencer, David Wattchow
Summary: Distinguishing and characterizing different classes of neurons in the enteric nervous system is a long-term goal for neuroscientists. While studies on enteric neurons in laboratory animals have been extensive, research on the human enteric nervous system is less advanced. Recent studies using single cell sequencing have made progress in classifying enteric neurons in mice and humans, but a comprehensive classification is yet to be achieved. This study presents preliminary data on a method to distinguish classes of myenteric neurons in the human colon using immunohistochemical, morphological, projection, and size data on single cells.
ENTERIC NERVOUS SYSTEM II
(2022)