Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing

Ageing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfu...

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Autores principales:	Dibesh Thapa, Joäo de Sousa Valente, Brentton Barrett, Matthew John Smith, Fulye Argunhan, Sheng Y Lee, Sofya Nikitochkina, Xenia Kodji, Susan D Brain
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	ageing TRPM8 TRPA1 cold response vascular response thermoregulation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/26ce2891ff7b4b918ed2630701c56e1e
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spelling	oai:doaj.org-article:26ce2891ff7b4b918ed2630701c56e1e2021-11-15T09:45:02ZDysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing10.7554/eLife.701532050-084Xe70153https://doaj.org/article/26ce2891ff7b4b918ed2630701c56e1e2021-11-01T00:00:00Zhttps://elifesciences.org/articles/70153https://doaj.org/toc/2050-084XAgeing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α2c adrenoceptor expression in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.Dibesh ThapaJoäo de Sousa ValenteBrentton BarrettMatthew John SmithFulye ArgunhanSheng Y LeeSofya NikitochkinaXenia KodjiSusan D BraineLife Sciences Publications LtdarticleageingTRPM8TRPA1cold responsevascular responsethermoregulationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ageing TRPM8 TRPA1 cold response vascular response thermoregulation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	ageing TRPM8 TRPA1 cold response vascular response thermoregulation Medicine R Science Q Biology (General) QH301-705.5 Dibesh Thapa Joäo de Sousa Valente Brentton Barrett Matthew John Smith Fulye Argunhan Sheng Y Lee Sofya Nikitochkina Xenia Kodji Susan D Brain Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
description	Ageing is associated with increased vulnerability to environmental cold exposure. Previously, we identified the role of the cold-sensitive transient receptor potential (TRP) A1, M8 receptors as vascular cold sensors in mouse skin. We hypothesised that this dynamic cold-sensor system may become dysfunctional in ageing. We show that behavioural and vascular responses to skin local environmental cooling are impaired with even moderate ageing, with reduced TRPM8 gene/protein expression especially. Pharmacological blockade of the residual TRPA1/TRPM8 component substantially diminished the response in aged, compared with young mice. This implies the reliance of the already reduced cold-induced vascular response in ageing mice on remaining TRP receptor activity. Moreover, sympathetic-induced vasoconstriction was reduced with downregulation of the α2c adrenoceptor expression in ageing. The cold-induced vascular response is important for sensing cold and retaining body heat and health. These findings reveal that cold sensors, essential for this neurovascular pathway, decline as ageing onsets.
format	article
author	Dibesh Thapa Joäo de Sousa Valente Brentton Barrett Matthew John Smith Fulye Argunhan Sheng Y Lee Sofya Nikitochkina Xenia Kodji Susan D Brain
author_facet	Dibesh Thapa Joäo de Sousa Valente Brentton Barrett Matthew John Smith Fulye Argunhan Sheng Y Lee Sofya Nikitochkina Xenia Kodji Susan D Brain
author_sort	Dibesh Thapa
title	Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
title_short	Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
title_full	Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
title_fullStr	Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
title_full_unstemmed	Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing
title_sort	dysfunctional trpm8 signalling in the vascular response to environmental cold in ageing
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/26ce2891ff7b4b918ed2630701c56e1e
work_keys_str_mv	AT dibeshthapa dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT joaodesousavalente dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT brenttonbarrett dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT matthewjohnsmith dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT fulyeargunhan dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT shengylee dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT sofyanikitochkina dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT xeniakodji dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing AT susandbrain dysfunctionaltrpm8signallinginthevascularresponsetoenvironmentalcoldinageing
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Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing

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