Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice

This is an open access article under the terms of the Creative Commons Attribution-Non Commercial-No Derivs License.

Detalles Bibliográficos
Autores: Alcalde, Ignacio, Íñigo-Portugués, Almudena, González-González, Omar, Almaraz, Laura, Artime, Enol, Morenilla-Palao, Cruz, Gallar, Juana, Viana, Félix, Merayo-Lloves, Jesús, Belmonte, Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/309215
Acceso en línea:http://hdl.handle.net/10261/309215
Access Level:acceso abierto
Palabra clave:Aging
Cold thermoreceptors
Dry eye
Pain
Tearing
Trigeminal ganglion
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dc.title.none.fl_str_mv Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
title Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
spellingShingle Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
Alcalde, Ignacio
Aging
Cold thermoreceptors
Dry eye
Pain
Tearing
Trigeminal ganglion
title_short Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
title_full Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
title_fullStr Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
title_full_unstemmed Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
title_sort Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in mice
dc.creator.none.fl_str_mv Alcalde, Ignacio
Íñigo-Portugués, Almudena
González-González, Omar
Almaraz, Laura
Artime, Enol
Morenilla-Palao, Cruz
Gallar, Juana
Viana, Félix
Merayo-Lloves, Jesús
Belmonte, Carlos
author Alcalde, Ignacio
author_facet Alcalde, Ignacio
Íñigo-Portugués, Almudena
González-González, Omar
Almaraz, Laura
Artime, Enol
Morenilla-Palao, Cruz
Gallar, Juana
Viana, Félix
Merayo-Lloves, Jesús
Belmonte, Carlos
author_role author
author2 Íñigo-Portugués, Almudena
González-González, Omar
Almaraz, Laura
Artime, Enol
Morenilla-Palao, Cruz
Gallar, Juana
Viana, Félix
Merayo-Lloves, Jesús
Belmonte, Carlos
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía, Industria y Competitividad (España)
Ministerio de Ciencia e Innovación (España)
Principado de Asturias
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Fundación Ramón Areces
Caja Rural de Asturias
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Aging
Cold thermoreceptors
Dry eye
Pain
Tearing
Trigeminal ganglion
topic Aging
Cold thermoreceptors
Dry eye
Pain
Tearing
Trigeminal ganglion
description This is an open access article under the terms of the Creative Commons Attribution-Non Commercial-No Derivs License.
publishDate 2018
dc.date.none.fl_str_mv 2018
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/309215
url http://hdl.handle.net/10261/309215
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/MINECO//SAF2014-54518-C3-1-R
info:eu-repo/grantAgreement/MINECO//SAF2014-54518-C3-2-R
info:eu-repo/grantAgreement/MINECO//SAF2016-77233-R
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Journal of Comparative Neurology
https://doi.org/10.1002/cne.24454
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dc.publisher.none.fl_str_mv Wiley-VCH
publisher.none.fl_str_mv Wiley-VCH
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Morphological and functional changes in TRPM8-expressing corneal cold thermoreceptor neurons during aging and their impact on tearing in miceAlcalde, IgnacioÍñigo-Portugués, AlmudenaGonzález-González, OmarAlmaraz, LauraArtime, EnolMorenilla-Palao, CruzGallar, JuanaViana, FélixMerayo-Lloves, JesúsBelmonte, CarlosAgingCold thermoreceptorsDry eyePainTearingTrigeminal ganglionThis is an open access article under the terms of the Creative Commons Attribution-Non Commercial-No Derivs License.Morphological and functional alterations of peripheral somatosensory neurons during the aging process lead to a decline of somatosensory perception. Here, we analyze the changes occurring with aging in trigeminal ganglion (TG), TRPM8-expressing cold thermoreceptor neurons innervating the mouse cornea, which participate in the regulation of basal tearing and blinking and have been implicated in the pathogenesis of dry eye disease (DED). TG cell bodies and axonal branches were examined in a mouse line (TRPM8BAC-EYFP) expressing a fluorescent reporter. In 3 months old animals, about 50% of TG cold thermoreceptor neurons were intensely fluorescent, likely providing strongly fluorescent axons and complex corneal nerve terminals with ongoing activity at 34°C and low-threshold, robust responses to cooling. The remaining TRPM8+ corneal axons were weakly fluorescent with nonbeaded axons, sparsely ramified nerve terminals, and exhibited a low-firing rate at 34°C, responding moderately to cooling pulses as do weakly fluorescent TG neurons. In aged (24 months) mice, the number of weakly fluorescent TG neurons was strikingly high while the morphology of TRPM8+ corneal axons changed drastically; 89% were weakly fluorescent, unbranched, and often ending in the basal epithelium. Functionally, 72.5% of aged cold terminals responded as those of young animals, but 27.5% exhibited very low-background activity and abnormal responsiveness to cooling pulses. These morpho-functional changes develop in parallel with an enhancement of tear's basal flow and osmolarity, suggesting that the aberrant sensory inflow to the brain from impaired peripheral cold thermoreceptors contributes to age-induced abnormal tearing and to the high incidence of DED in elderly people.This work was supported by grants FC-15-GRUPIN14–141 (Consejería de Economía y Empleo, Asturias, Spain), Fundación Ramón Areces, Caja Rural de Asturias, SAF2014–54518-C3-2-R, SAF2014–54518-C3-1-R, SAF2017–83674-C2-2-R, SAF2017–83674-C2-1-R, and SAF2016–77233-R (Ministerio de Economía, Industria y Competitividad, Spain and European Regional Development Funds, European Union), and “Severo Ochoa” Program for Centers of Excellence in R&D (SEV-2013-0317).Peer reviewedWiley-VCHMinisterio de Economía, Industria y Competitividad (España)Ministerio de Ciencia e Innovación (España)Principado de AsturiasMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Fundación Ramón ArecesCaja Rural de AsturiasConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/309215reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//SAF2014-54518-C3-1-Rinfo:eu-repo/grantAgreement/MINECO//SAF2014-54518-C3-2-Rinfo:eu-repo/grantAgreement/MINECO//SAF2016-77233-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-83674-C2-1-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-83674-C2-2-Rinfo:eu-repo/grantAgreement/MINECO//SEV-2013-0317Journal of Comparative Neurologyhttps://doi.org/10.1002/cne.24454Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3092152026-05-22T06:33:51Z
score 15,81155

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