Dysfunctional TRPM8 signalling in the vascular response to environmental cold in ageing.
Elife
; 102021 11 02.
Article
em En
| MEDLINE
| ID: mdl-34726597
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.
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Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Temperatura Baixa
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Canais de Cátion TRPM
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Canal de Cátion TRPA1
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article