Research output: Contribution to journal › Article › peer-review
Dibesh Thapa, Joao Sousa-Valente, Brentton Barrett, Matthew Smith, Fulye Argunhan, Sheng Y Lee, Sofya Nikitochkina , Xenia Kodji, Susan Brain
Original language | English |
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Article number | e70153 |
Journal | eLife |
Volume | 10 |
Early online date | 2 Nov 2021 |
DOIs | |
Accepted/In press | 2 Nov 2021 |
E-pub ahead of print | 2 Nov 2021 |
Published | Nov 2021 |
Additional links |
Dysfunctional TRPM8 signalling in_Accepted2November2021_GOLD VoR (CC BY)
elife_70153_v2_1_.pdf, 4.26 MB, application/pdf
Uploaded date:15 Nov 2021
Version:Final published version
Licence:CC BY
Ageing is associated with increased vulnerability to environmental cold exposure. Previ-ously, 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 α 2c adre-noceptor 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 neuro-vascular pathway, decline as ageing onsets.
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