Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.
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Authors
Valente, Joäo de Sousa
Barrett, Brentton
Smith, Matthew John
Argunhan, Fulye
Lee, Sheng Y
Nikitochkina, Sofya
Kodji, Xenia
Publication Date
2021-11-02Journal Title
Elife
ISSN
2050-084X
Publisher
eLife Sciences Publications, Ltd
Volume
10
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Thapa, D., Valente, J. d. S., Barrett, B., Smith, M. J., Argunhan, F., Lee, S. Y., Nikitochkina, S., et al. (2021). Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.. Elife, 10 https://doi.org/10.7554/eLife.70153
Abstract
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.
Keywords
TRPA1, TRPM8, ageing, biochemistry, chemical biology, cold response, mouse, thermoregulation, vascular response, Aging, Animals, Blood Circulation, Cold Temperature, Female, Mice, Nociception, Signal Transduction, Skin, TRPA1 Cation Channel, TRPM Cation Channels
Sponsorship
Versus Arthritis (ARUK21524)
British Heart Foundation (PG/12/34/29557, FS/19/42/34527)
Biotechnology and Biological Sciences Research Council (BB/P005616/1)
Identifiers
PMC8592571, 34726597
External DOI: https://doi.org/10.7554/eLife.70153
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332204
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