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

Thapa, Dibesh; Valente, João de Sousa; Barrett, Brentton; Smith, Matthew John; Argunhan, Fulye; Lee, Sheng Y; Nikitochkina, Sofya; Kodji, Xenia; Brain, Susan D.

doi:10.7554/elife.70153

Cited by 14 publications

(9 citation statements)

References 63 publications

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“…Accordingly, TRPM8 knockouts cannot discriminate between warm and cool stimuli; in addition, they do not exhibit inflammatory or neuropathic cold allodynia, a painful sequelae of cancer chemotherapies [12]. These knockout mice also tend to develop obesity due to day-time hyperphagia; and ageing wildtypes, showing reduced TRPM8 expression and function, cannot properly prevent heat loss by vasoconstriction in cool environment [141,168]. Vice versa, TRPM8 agonist treatment in wildtypes leads to enhanced energy expenditure and loss of body weight [39].…”

Section: Price Worthy Trps Trpv3 and Trpm8mentioning

confidence: 99%

Nobel somatosensations and pain

Reeh

Fischer

2022

Pflugers Arch - Eur J Physiol

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The Nobel prices 2021 for Physiology and Medicine have been awarded to David Julius and Ardem Patapoutian "for their discoveries of receptors for temperature and touch", TRPV1 and PIEZO1/2. The present review tells the past history of the capsaicin receptor, covers further selected TRP channels, TRPA1 in particular, and deals with mechanosensitivity in general and mechanical hyperalgesia in particular. Other achievements of the laureates and translational aspects of their work are shortly treated.

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Section: Price Worthy Trps Trpv3 and Trpm8mentioning

confidence: 99%

Nobel somatosensations and pain

Reeh

Fischer

2022

Pflugers Arch - Eur J Physiol

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“…For example, in case of the heat-sensitive transient receptor potential vanilloid-1 channel, the Q 10 value is 40 in the temperature range between 41 and 50 °C [ 35 ], while, for the cold-sensitive transient receptor potential melastatin-8, the calculated Q 10 was 24 between 18 and 25 °C [ 36 ]. Importantly, both aforementioned temperature-sensitive channels were shown to play important roles in the mediation of vascular responses in the skin [ 20 , 37 ]. With in-silico methods, it is extremely difficult, if not impossible, to predict how temperature-dependent changes in molecular functions would affect physiological responses of different tissues or organs.…”

Section: Discussionmentioning

confidence: 99%

Stereolithography 3D Printing of a Heat Exchanger for Advanced Temperature Control in Wire Myography

et al. 2022

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We report the additive manufacturing of a heat-exchange device that can be used as a cooling accessory in a wire myograph. Wire myography is used for measuring vasomotor responses in small resistance arteries; however, the commercially available devices are not capable of active cooling. Here, we critically evaluated a transparent resin material, in terms of mechanical, structural, and thermal behavior. Tensile strength tests (67.66 ± 1.31 MPa), Charpy impact strength test (20.70 ± 2.30 kJ/m2), and Shore D hardness measurements (83.0 ± 0.47) underlined the mechanical stability of the material, supported by digital microscopy, which revealed a glass-like structure. Differential scanning calorimetry with thermogravimetry analysis and thermal conductivity measurements showed heat stability until ~250 °C and effective heat insulation. The 3D-printed heat exchanger was tested in thermophysiology experiments measuring the vasomotor responses of rat tail arteries at different temperatures (13, 16, and 36 °C). The heat-exchange device was successfully used as an accessory of the wire myograph system to cool down the experimental chambers and steadily maintain the targeted temperatures. We observed temperature-dependent differences in the vasoconstriction induced by phenylephrine and KCl. In conclusion, the transparent resin material can be used in additive manufacturing of heat-exchange devices for biomedical research, such as wire myography. Our animal experiments underline the importance of temperature-dependent physiological mechanisms, which should be further studied to understand the background of the thermal changes and their consequences.

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“…TRPA1 and TRPM8 receptors have important roles in the molecular sensing of environmental cold but their precise mechanisms remain unclear. We have been interested in the effect of pharmacological antagonists on the maintenance of a healthy response to the cold, principally concentrating on the vascular response to local cold exposure in skin to date [9,34,35]. Here, we have extended our studies to whole body cooling.…”

Section: Discussionmentioning

confidence: 99%

Influence of Cold-TRP Receptors on Cold-Influenced Behaviour

et al. 2021

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The transient receptor potential (TRP) channels, TRPA1 and TRPM8, are thermo-receptors that detect cold and cool temperatures and play pivotal roles in mediating the cold-induced vascular response. In this study, we investigated the role of TRPA1 and TRPM8 in the thermoregulatory behavioural responses to environmental cold exposure by measuring core body temperature and locomotor activity using a telemetry device that was surgically implanted in mice. The core body temperature of mice that were cooled at 4 °C over 3 h was increased and this was accompanied by an increase in UCP-1 and TRPM8 level as detected by Western blot. We then established an effective route, by which the TRP antagonists could be administered orally with palatable food. This avoids the physical restraint of mice, which is crucial as that could influence the behavioural results. Using selective pharmacological antagonists A967079 and AMTB for TRPA1 and TRPM8 receptors, respectively, we show that TRPM8, but not TRPA1, plays a direct role in thermoregulation response to whole body cold exposure in the mouse. Additionally, we provide evidence of increased TRPM8 levels after cold exposure which could be a protective response to increase core body temperature to counter cold.

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

Cited by 14 publications

References 63 publications

Nobel somatosensations and pain

Nobel somatosensations and pain

Stereolithography 3D Printing of a Heat Exchanger for Advanced Temperature Control in Wire Myography

Influence of Cold-TRP Receptors on Cold-Influenced Behaviour

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