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Article ; Online: Fresh perspectives on how to build, maintain and repair the ENS.

Boesmans, Werend

Nature reviews. Gastroenterology & hepatology

2023 Volume 21, Issue 2, Page(s) 82–83

Language	English
Publishing date	2023-11-17
Publishing country	England
Document type	Journal Article
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-023-00870-4
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Article ; Online: Editorial introduction for special issue on enteric glia.

Gulbransen, Brian D / Boesmans, Werend

Neuroscience letters

2023 Volume 814, Page(s) 137462

MeSH term(s)	Neuroglia ; Enteric Nervous System
Language	English
Publishing date	2023-08-23
Publishing country	Ireland
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2023.137462
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Article ; Online: Mini-review: Enteric glial cell heterogeneity: Is it all about the niche?

Sanchini, Gabriele / Vaes, Nathalie / Boesmans, Werend

Neuroscience letters

2023 Volume 812, Page(s) 137396

Abstract: Enteric glial cells represent the enteric population of peripheral glia. According to their 'glial' nature, their principal function is to support enteric neurons in both structural and functional ways. Mounting evidence however demonstrates that enteric ...

Abstract	Enteric glial cells represent the enteric population of peripheral glia. According to their 'glial' nature, their principal function is to support enteric neurons in both structural and functional ways. Mounting evidence however demonstrates that enteric glial cells crucially contribute to the majority of enteric nervous system functions, thus acting as pivotal players in the maintenance of gut homeostasis. Various types of enteric glia are present within the gut wall, creating an intricate interaction network with other gastrointestinal cell types. Their distribution throughout the different layers of the gut wall translates in characteristic phenotypes that are tailored to the local tissue requirements of the digestive tract. This heterogeneity is assumed to be mirrored by functional specialization, but the extensive plasticity and versatility of enteric glial cells complicates a one on one phenotype/function definition. Moreover, the relative contribution of niche-specific signals versus lineage determinants for driving enteric glial heterogeneity is still uncertain. In this review we focus on the current understanding of phenotypic and functional enteric glial cell heterogeneity, from a microenvironmental and developmental perspective.
MeSH term(s)	Neuroglia/metabolism ; Neurons/metabolism ; Enteric Nervous System/metabolism ; Phenotype
Language	English
Publishing date	2023-07-12
Publishing country	Ireland
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2023.137396
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Article ; Online: The enteric nervous system: the hub in a star network.

Bon-Frauches, Ana Carina / Boesmans, Werend

Nature reviews. Gastroenterology & hepatology

2020 Volume 17, Issue 12, Page(s) 717–718

MeSH term(s)	Animals ; Enteric Nervous System ; Humans ; Intestine, Small ; Mice
Language	English
Publishing date	2020-10-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-020-00377-2
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Article ; Online: An optimization and refinement of the whole-gut transit assay in mice.

Schonkeren, Simone L / Seeldrayers, Saskia / Thijssen, Meike S / Boesmans, Werend / Langen, Ramon C J / Melotte, Veerle

Neurogastroenterology and motility

2023 Volume 35, Issue 8, Page(s) e14586

Abstract: Background: Gastrointestinal motility measurements in mice are currently performed under suboptimal conditions, as these nocturnal animals are measured during light conditions. In addition, other stressors, like individual housing, placement in a new ... ...

Abstract	Background: Gastrointestinal motility measurements in mice are currently performed under suboptimal conditions, as these nocturnal animals are measured during light conditions. In addition, other stressors, like individual housing, placement in a new cage during observation, and lack of bedding and cage enrichment cause animal discomfort and might contribute to higher variability. Here we aimed to develop a refined method of the widely-used whole-gut transit assay. Methods: Wildtype mice (N = 24) were subjected to the standard or refined whole-gut transit assay, either with or without a standardized slowing in gastrointestinal motility induced by loperamide. The standard assay consisted of a gavage with carmine red, observation during the light period and individual housing in a new cage without cage enrichment. For the refined whole-gut transit assay, mice were gavaged with UV-fluorescent DETEX®, observed during the dark period, while pairwise housed in their home cage with cage enrichment. Time until excretion of the first colored fecal pellet was assessed, and pellets were collected to assess number, weight, and water content. Key results: The DETEX®-containing pellets were UV-detectable, allowing to measure the mice in their active period in the dark. The refined method caused less variation (20.8% and 16.0%) compared to the standard method (29.0% and 21.7%). Fecal pellet number, weight, and water content was significantly different between the standard and refined method. Conclusions & inferences: This refined whole-gut transit assay provides a reliable approach to measure whole-gut transit time in mice in a more physiological context, with reduced variability compared to the standard method.
MeSH term(s)	Mice ; Animals ; Gastrointestinal Motility/physiology ; Feces ; Loperamide/pharmacology ; Water ; Gastrointestinal Transit/physiology
Chemical Substances	Loperamide (6X9OC3H4II) ; Water (059QF0KO0R)
Language	English
Publishing date	2023-04-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14586
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Article ; Online: Chemogenetic versus recombination-driven manipulation of enteric glia.

Boesmans, Werend / Vanden Berghe, Pieter

The Journal of physiology

2017 Volume 595, Issue 11, Page(s) 3255–3256

MeSH term(s)	Animals ; Colon ; Intestine, Small ; Mice ; Neuroglia ; Permeability ; Recombination, Genetic
Language	English
Publishing date	2017-05-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP273975
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Article: Development, Diversity, and Neurogenic Capacity of Enteric Glia.

Boesmans, Werend / Nash, Amelia / Tasnády, Kinga R / Yang, Wendy / Stamp, Lincon A / Hao, Marlene M

Frontiers in cell and developmental biology

2022 Volume 9, Page(s) 775102

Abstract: Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the "support" cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They ... ...

Abstract	Enteric glia are a fascinating population of cells. Initially identified in the gut wall as the "support" cells of the enteric nervous system, studies over the past 20 years have unveiled a vast array of functions carried out by enteric glia. They mediate enteric nervous system signalling and play a vital role in the local regulation of gut functions. Enteric glial cells interact with other gastrointestinal cell types such as those of the epithelium and immune system to preserve homeostasis, and are perceptive to luminal content. Their functional versatility and phenotypic heterogeneity are mirrored by an extensive level of plasticity, illustrated by their reactivity in conditions associated with enteric nervous system dysfunction and disease. As one of the hallmarks of their plasticity and extending their operative relationship with enteric neurons, enteric glia also display neurogenic potential. In this review, we focus on the development of enteric glial cells, and the mechanisms behind their heterogeneity in the adult gut. In addition, we discuss what is currently known about the role of enteric glia as neural precursors in the enteric nervous system.
Language	English
Publishing date	2022-01-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2021.775102
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Article ; Online: Nerves in gastrointestinal cancer: from mechanism to modulations.

Vaes, Nathalie / Idris, Musa / Boesmans, Werend / Alves, Maria M / Melotte, Veerle

Nature reviews. Gastroenterology & hepatology

2022 Volume 19, Issue 12, Page(s) 768–784

Abstract: Maintenance of gastrointestinal health is challenging as it requires balancing multifaceted processes within the highly complex and dynamic ecosystem of the gastrointestinal tract. Disturbances within this vibrant environment can have detrimental ... ...

Abstract	Maintenance of gastrointestinal health is challenging as it requires balancing multifaceted processes within the highly complex and dynamic ecosystem of the gastrointestinal tract. Disturbances within this vibrant environment can have detrimental consequences, including the onset of gastrointestinal cancers. Globally, gastrointestinal cancers account for ~19% of all cancer cases and ~22.5% of all cancer-related deaths. Developing new ways to more readily detect and more efficiently target these malignancies are urgently needed. Whereas members of the tumour microenvironment, such as immune cells and fibroblasts, have already been in the spotlight as key players of cancer initiation and progression, the importance of the nervous system in gastrointestinal cancers has only been highlighted in the past few years. Although extrinsic innervations modulate gastrointestinal cancers, cells and signals from the gut's intrinsic innervation also have the ability to do so. Here, we shed light on this thriving field and discuss neural influences during gastrointestinal carcinogenesis. We focus on the interactions between neurons and components of the gastrointestinal tract and tumour microenvironment, on the neural signalling pathways involved, and how these factors affect the cancer hallmarks, and discuss the neural signatures in gastrointestinal cancers. Finally, we highlight neural-related therapies that have potential for the management of gastrointestinal cancers.
MeSH term(s)	Humans ; Ecosystem ; Gastrointestinal Neoplasms/etiology ; Gastrointestinal Neoplasms/pathology ; Tumor Microenvironment/physiology ; Signal Transduction ; Carcinogenesis
Language	English
Publishing date	2022-09-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2493722-8
ISSN	1759-5053 ; 1759-5045
ISSN (online)	1759-5053
ISSN	1759-5045
DOI	10.1038/s41575-022-00669-9
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Article ; Online: Differences in enteric neuronal density in the NSE-Noggin mouse model across institutes.

Schonkeren, Simone L / Thijssen, Meike S / Idris, Musa / Wouters, Kim / de Vaan, Joëlle / Teubner, Andreas / Gijbels, Marion J / Boesmans, Werend / Melotte, Veerle

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3686

Abstract: The enteric nervous system (ENS) is a large and complex part of the peripheral nervous system, and it is vital for gut homeostasis. To study the ENS, different hyper- and hypo-innervated model systems have been developed. The NSE-Noggin mouse model was ... ...

Abstract	The enteric nervous system (ENS) is a large and complex part of the peripheral nervous system, and it is vital for gut homeostasis. To study the ENS, different hyper- and hypo-innervated model systems have been developed. The NSE-Noggin mouse model was described as one of the few models with a higher enteric neuronal density in the colon. However, in our hands NSE-Noggin mice did not present with a hyperganglionic phenotype. NSE-Noggin mice were phenotyped based on fur appearance, genotyped and DNA sequenced to demonstrate transgene and intact NSE-Noggin-IRES-EGFP construct presence, and RNA expression of Noggin was shown to be upregulated. Positive EGFP staining in the plexus of NSE-Noggin mice also confirmed Noggin protein expression. Myenteric plexus preparations of the colon were examined to quantify both the overall density of enteric neurons and the proportions of enteric neurons expressing specific subtype markers. The total number of enteric neurons in the colonic myenteric plexus of transgenic mice did not differ significantly from wild types, nor did the proportion of calbindin, calretinin, or serotonin immunoreactive myenteric neurons. Possible reasons as to why the hyperinnervated phenotype could not be observed in contrast with original studies using this mouse model are discussed, including study design, influence of microbiota, and other environmental variables.
MeSH term(s)	Mice ; Animals ; Neurons/metabolism ; Enteric Nervous System/metabolism ; Carrier Proteins/metabolism ; Myenteric Plexus ; Mice, Transgenic ; Colon
Chemical Substances	noggin protein (148294-77-3) ; Carrier Proteins
Language	English
Publishing date	2024-02-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-54337-w
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Article ; Online: Simultaneous whole-cell patch-clamp and calcium imaging on myenteric neurons.

Li, Zhiling / Boesmans, Werend / Kazwiny, Youcef / Hao, Marlene M / Vanden Berghe, Pieter

American journal of physiology. Gastrointestinal and liver physiology

2022 Volume 323, Issue 4, Page(s) G341–G347

Abstract: Live calcium imaging is often used as a proxy for electrophysiological measurements and has been a valuable tool that allows simultaneous analysis of neuronal activity in multiple cells at the population level. In the enteric nervous system, there are ... ...

Abstract	Live calcium imaging is often used as a proxy for electrophysiological measurements and has been a valuable tool that allows simultaneous analysis of neuronal activity in multiple cells at the population level. In the enteric nervous system, there are two main electrophysiological classes of neurons, after-hyperpolarizing (AH)- and synaptic (S)-neurons, which have been shown to have different calcium handling mechanisms. However, they are rarely considered separately in calcium imaging experiments. A handful of studies have shown that in guinea pig, a calcium transient will accompany a single action potential in AH-neurons, but multiple action potentials are required to generate a calcium transient in S-neurons. How this translates to different modes of cellular depolarization and whether this is consistent across species is unknown. In this study, we used simultaneous whole-cell patch-clamp electrophysiology together with calcium imaging to investigate how enteric neurons respond to different modes of depolarization. Using both traditional (4 Hz) and also high-speed (1,000 Hz) imaging techniques, we found that single action potentials elicit calcium transients in both AH-neurons and S-neurons. Subthreshold membrane depolarizations were also able to elicit calcium transients, although calcium responses were generally amplified if an action potential was present. Furthermore, we identified that responses to nicotinic acetylcholine receptor stimulation can be used to distinguish between AH- and S-neurons in calcium imaging.NEW & NOTEWORTHY Live calcium imaging is an important tool for investigating enteric nervous system (ENS) function. Previous studies have shown that multiple action potentials are needed to generate a calcium response in S-neurons, which has important implications for the interpretation of calcium imaging data. Here, we show that in mouse myenteric neurons, calcium transients are elicited by single action potentials in both AH- and S-neurons. In addition, nicotinic acetylcholine receptor stimulation can be used to distinguish between these two classes.
MeSH term(s)	Action Potentials/physiology ; Animals ; Calcium ; Electrophysiology ; Guinea Pigs ; Humans ; Mice ; Myenteric Plexus ; Neurons/physiology ; Receptors, Nicotinic
Chemical Substances	Receptors, Nicotinic ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-08-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00162.2022
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