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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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/70153 |
| _version_ | 1811180463794946048 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T09:03:35Z |
| format | Article |
| id | doaj.art-26ce2891ff7b4b918ed2630701c56e1e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:03:35Z |
| publishDate | 2021-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-26ce2891ff7b4b918ed2630701c56e1e2022-12-22T04:32:42ZengeLife Sciences Publications LtdeLife2050-084X2021-11-011010.7554/eLife.70153Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageingDibesh Thapa0https://orcid.org/0000-0002-7435-5483Joäo de Sousa Valente1Brentton Barrett2Matthew John Smith3Fulye Argunhan4Sheng Y Lee5Sofya Nikitochkina6Xenia Kodji7Susan D Brain8https://orcid.org/0000-0002-9684-8342Section of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United KingdomSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United KingdomSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United KingdomSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United KingdomSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United KingdomSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United Kingdom; Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge, United KingdomSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United KingdomSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United Kingdom; Skin Research Institute, Agency of Science, Technology, and Research (A*STAR), Singapore, SingaporeSection of Vascular Biology and Inflammation, School of Cardiovascular Medicine and Sciences, BHF Centre of Research Excellence, King’s College London, London, United KingdomAgeing 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.https://elifesciences.org/articles/70153ageingTRPM8TRPA1cold responsevascular responsethermoregulation |
| spellingShingle | 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 eLife ageing TRPM8 TRPA1 cold response vascular response thermoregulation |
| title | 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_short | 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 |
| topic | ageing TRPM8 TRPA1 cold response vascular response thermoregulation |
| url | https://elifesciences.org/articles/70153 |
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