Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum
- Autores
- Guo, Tiantian; Patel, Shivam P; Shah, Dhruv; Chi, Ling; Emadi, Sharareh; Pierce, David M.; Han, Martin; Brumovsky, Pablo Rodolfo; Feng, Bin
- Año de publicación
- 2021
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Colorectal hypersensitivity and sensitization of both mechanosensitive and mechanically insensitive afferents develop after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in the mouse, a model of postinfectious irritable bowel syndrome. In mice in which 80% of extrinsic colorectal afferents were labeled genetically using the promotor for vesicular glutamate transporter type 2 (VGLUT2), we systematically quantified the morphology of VGLUT2-positive axons in mouse colorectum 7–28 days following intracolonic TNBS treatment. After removal, the colorectum was distended (20 mmHg), fixed with paraformaldehyde, and optically cleared to image VGLUT2-positive axons throughout the colorectal wall thickness. We conducted vector path tracing of individual axons to allow systematic quantification of nerve fiber density and shape. Abundant VGLUT2-positive nerve fibers were present in most layers of the colorectum, except the serosal and longitudinal muscular layers. A small percentage of VGLUT2-positive myenteric plexus neurons was also detected. Intracolonic TNBS treatment significantly reduced the number of VGLUT2-positive nerve fibers in submucosal, myenteric plexus, and mucosal layers at day 7 post-TNBS, which mostly recovered by day 28. We also found that almost all fibers in the submucosa were meandering and curvy, with 10% showing pronounced curviness (quantified by the linearity index). TNBS treatment resulted in a significant reduction of the proportions of pronounced curvy fibers in the rectal region at 28 days post-TNBS. Altogether, the present morphological study reveals profound changes in the distribution of VGLUT2-positive fibers in mouse colorectum undergoing TNBS-induced colitis and draws attention to curvy fibers in the submucosa with potential roles in visceral nociception. NEW & NOTEWORTHY We conducted genetic labeling and optical clearing to visualize extrinsic sensory nerve fibers in whole-mount colorectum, which revealed widespread presence of axons in the submucosal layer. Remarkably, axons in the submucosa were meandering and curvy, in contrast to axons in other layers generally aligned with the basal tissues. Intracolonic TNBS treatment led to pronounced changes of nerve fiber density and curviness, suggesting nerve fiber morphologies as potentially contributing factors to sensory sensitization.
Fil: Guo, Tiantian. University of Connecticut; Estados Unidos
Fil: Patel, Shivam P. University of Connecticut; Estados Unidos
Fil: Shah, Dhruv. University of Connecticut; Estados Unidos
Fil: Chi, Ling. University of Connecticut; Estados Unidos
Fil: Emadi, Sharareh. University of Connecticut; Estados Unidos
Fil: Pierce, David M.. University of Connecticut; Estados Unidos
Fil: Han, Martin. University of Connecticut; Estados Unidos
Fil: Brumovsky, Pablo Rodolfo. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina
Fil: Feng, Bin. University of Connecticut; Estados Unidos - Materia
-
AFFERENT SENSITIZATION
CHANNELRHODOPSIN
COLORECTUM
OPTICAL TISSUE CLEARING
VGLUT2-CRE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/163897
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Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectumGuo, TiantianPatel, Shivam PShah, DhruvChi, LingEmadi, ShararehPierce, David M.Han, MartinBrumovsky, Pablo RodolfoFeng, BinAFFERENT SENSITIZATIONCHANNELRHODOPSINCOLORECTUMOPTICAL TISSUE CLEARINGVGLUT2-CREhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Colorectal hypersensitivity and sensitization of both mechanosensitive and mechanically insensitive afferents develop after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in the mouse, a model of postinfectious irritable bowel syndrome. In mice in which 80% of extrinsic colorectal afferents were labeled genetically using the promotor for vesicular glutamate transporter type 2 (VGLUT2), we systematically quantified the morphology of VGLUT2-positive axons in mouse colorectum 7–28 days following intracolonic TNBS treatment. After removal, the colorectum was distended (20 mmHg), fixed with paraformaldehyde, and optically cleared to image VGLUT2-positive axons throughout the colorectal wall thickness. We conducted vector path tracing of individual axons to allow systematic quantification of nerve fiber density and shape. Abundant VGLUT2-positive nerve fibers were present in most layers of the colorectum, except the serosal and longitudinal muscular layers. A small percentage of VGLUT2-positive myenteric plexus neurons was also detected. Intracolonic TNBS treatment significantly reduced the number of VGLUT2-positive nerve fibers in submucosal, myenteric plexus, and mucosal layers at day 7 post-TNBS, which mostly recovered by day 28. We also found that almost all fibers in the submucosa were meandering and curvy, with 10% showing pronounced curviness (quantified by the linearity index). TNBS treatment resulted in a significant reduction of the proportions of pronounced curvy fibers in the rectal region at 28 days post-TNBS. Altogether, the present morphological study reveals profound changes in the distribution of VGLUT2-positive fibers in mouse colorectum undergoing TNBS-induced colitis and draws attention to curvy fibers in the submucosa with potential roles in visceral nociception. NEW & NOTEWORTHY We conducted genetic labeling and optical clearing to visualize extrinsic sensory nerve fibers in whole-mount colorectum, which revealed widespread presence of axons in the submucosal layer. Remarkably, axons in the submucosa were meandering and curvy, in contrast to axons in other layers generally aligned with the basal tissues. Intracolonic TNBS treatment led to pronounced changes of nerve fiber density and curviness, suggesting nerve fiber morphologies as potentially contributing factors to sensory sensitization.Fil: Guo, Tiantian. University of Connecticut; Estados UnidosFil: Patel, Shivam P. University of Connecticut; Estados UnidosFil: Shah, Dhruv. University of Connecticut; Estados UnidosFil: Chi, Ling. University of Connecticut; Estados UnidosFil: Emadi, Sharareh. University of Connecticut; Estados UnidosFil: Pierce, David M.. University of Connecticut; Estados UnidosFil: Han, Martin. University of Connecticut; Estados UnidosFil: Brumovsky, Pablo Rodolfo. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Feng, Bin. University of Connecticut; Estados UnidosAmerican Physiological Society2021-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/163897Guo, Tiantian; Patel, Shivam P; Shah, Dhruv; Chi, Ling; Emadi, Sharareh; et al.; Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum; American Physiological Society; American Journal of Physiology-gastrointestinal and Liver Physiology; 320; 4; 4-2021; 1-140193-1857CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/10.1152/ajpgi.00363.2020info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpgi.00363.2020info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:19:03Zoai:ri.conicet.gov.ar:11336/163897instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:19:03.584CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum |
title |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum |
spellingShingle |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum Guo, Tiantian AFFERENT SENSITIZATION CHANNELRHODOPSIN COLORECTUM OPTICAL TISSUE CLEARING VGLUT2-CRE |
title_short |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum |
title_full |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum |
title_fullStr |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum |
title_full_unstemmed |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum |
title_sort |
Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum |
dc.creator.none.fl_str_mv |
Guo, Tiantian Patel, Shivam P Shah, Dhruv Chi, Ling Emadi, Sharareh Pierce, David M. Han, Martin Brumovsky, Pablo Rodolfo Feng, Bin |
author |
Guo, Tiantian |
author_facet |
Guo, Tiantian Patel, Shivam P Shah, Dhruv Chi, Ling Emadi, Sharareh Pierce, David M. Han, Martin Brumovsky, Pablo Rodolfo Feng, Bin |
author_role |
author |
author2 |
Patel, Shivam P Shah, Dhruv Chi, Ling Emadi, Sharareh Pierce, David M. Han, Martin Brumovsky, Pablo Rodolfo Feng, Bin |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
AFFERENT SENSITIZATION CHANNELRHODOPSIN COLORECTUM OPTICAL TISSUE CLEARING VGLUT2-CRE |
topic |
AFFERENT SENSITIZATION CHANNELRHODOPSIN COLORECTUM OPTICAL TISSUE CLEARING VGLUT2-CRE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Colorectal hypersensitivity and sensitization of both mechanosensitive and mechanically insensitive afferents develop after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in the mouse, a model of postinfectious irritable bowel syndrome. In mice in which 80% of extrinsic colorectal afferents were labeled genetically using the promotor for vesicular glutamate transporter type 2 (VGLUT2), we systematically quantified the morphology of VGLUT2-positive axons in mouse colorectum 7–28 days following intracolonic TNBS treatment. After removal, the colorectum was distended (20 mmHg), fixed with paraformaldehyde, and optically cleared to image VGLUT2-positive axons throughout the colorectal wall thickness. We conducted vector path tracing of individual axons to allow systematic quantification of nerve fiber density and shape. Abundant VGLUT2-positive nerve fibers were present in most layers of the colorectum, except the serosal and longitudinal muscular layers. A small percentage of VGLUT2-positive myenteric plexus neurons was also detected. Intracolonic TNBS treatment significantly reduced the number of VGLUT2-positive nerve fibers in submucosal, myenteric plexus, and mucosal layers at day 7 post-TNBS, which mostly recovered by day 28. We also found that almost all fibers in the submucosa were meandering and curvy, with 10% showing pronounced curviness (quantified by the linearity index). TNBS treatment resulted in a significant reduction of the proportions of pronounced curvy fibers in the rectal region at 28 days post-TNBS. Altogether, the present morphological study reveals profound changes in the distribution of VGLUT2-positive fibers in mouse colorectum undergoing TNBS-induced colitis and draws attention to curvy fibers in the submucosa with potential roles in visceral nociception. NEW & NOTEWORTHY We conducted genetic labeling and optical clearing to visualize extrinsic sensory nerve fibers in whole-mount colorectum, which revealed widespread presence of axons in the submucosal layer. Remarkably, axons in the submucosa were meandering and curvy, in contrast to axons in other layers generally aligned with the basal tissues. Intracolonic TNBS treatment led to pronounced changes of nerve fiber density and curviness, suggesting nerve fiber morphologies as potentially contributing factors to sensory sensitization. Fil: Guo, Tiantian. University of Connecticut; Estados Unidos Fil: Patel, Shivam P. University of Connecticut; Estados Unidos Fil: Shah, Dhruv. University of Connecticut; Estados Unidos Fil: Chi, Ling. University of Connecticut; Estados Unidos Fil: Emadi, Sharareh. University of Connecticut; Estados Unidos Fil: Pierce, David M.. University of Connecticut; Estados Unidos Fil: Han, Martin. University of Connecticut; Estados Unidos Fil: Brumovsky, Pablo Rodolfo. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; Argentina Fil: Feng, Bin. University of Connecticut; Estados Unidos |
description |
Colorectal hypersensitivity and sensitization of both mechanosensitive and mechanically insensitive afferents develop after intracolonic instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) in the mouse, a model of postinfectious irritable bowel syndrome. In mice in which 80% of extrinsic colorectal afferents were labeled genetically using the promotor for vesicular glutamate transporter type 2 (VGLUT2), we systematically quantified the morphology of VGLUT2-positive axons in mouse colorectum 7–28 days following intracolonic TNBS treatment. After removal, the colorectum was distended (20 mmHg), fixed with paraformaldehyde, and optically cleared to image VGLUT2-positive axons throughout the colorectal wall thickness. We conducted vector path tracing of individual axons to allow systematic quantification of nerve fiber density and shape. Abundant VGLUT2-positive nerve fibers were present in most layers of the colorectum, except the serosal and longitudinal muscular layers. A small percentage of VGLUT2-positive myenteric plexus neurons was also detected. Intracolonic TNBS treatment significantly reduced the number of VGLUT2-positive nerve fibers in submucosal, myenteric plexus, and mucosal layers at day 7 post-TNBS, which mostly recovered by day 28. We also found that almost all fibers in the submucosa were meandering and curvy, with 10% showing pronounced curviness (quantified by the linearity index). TNBS treatment resulted in a significant reduction of the proportions of pronounced curvy fibers in the rectal region at 28 days post-TNBS. Altogether, the present morphological study reveals profound changes in the distribution of VGLUT2-positive fibers in mouse colorectum undergoing TNBS-induced colitis and draws attention to curvy fibers in the submucosa with potential roles in visceral nociception. NEW & NOTEWORTHY We conducted genetic labeling and optical clearing to visualize extrinsic sensory nerve fibers in whole-mount colorectum, which revealed widespread presence of axons in the submucosal layer. Remarkably, axons in the submucosa were meandering and curvy, in contrast to axons in other layers generally aligned with the basal tissues. Intracolonic TNBS treatment led to pronounced changes of nerve fiber density and curviness, suggesting nerve fiber morphologies as potentially contributing factors to sensory sensitization. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-04 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/163897 Guo, Tiantian; Patel, Shivam P; Shah, Dhruv; Chi, Ling; Emadi, Sharareh; et al.; Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum; American Physiological Society; American Journal of Physiology-gastrointestinal and Liver Physiology; 320; 4; 4-2021; 1-14 0193-1857 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/163897 |
identifier_str_mv |
Guo, Tiantian; Patel, Shivam P; Shah, Dhruv; Chi, Ling; Emadi, Sharareh; et al.; Optical clearing reveals TNBS-induced morphological changes of VGLUT2-positive nerve fibers in mouse colorectum; American Physiological Society; American Journal of Physiology-gastrointestinal and Liver Physiology; 320; 4; 4-2021; 1-14 0193-1857 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/10.1152/ajpgi.00363.2020 info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpgi.00363.2020 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Physiological Society |
publisher.none.fl_str_mv |
American Physiological Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844614158696316928 |
score |
13.070432 |