Thiazoline-related TRPA1 agonist odorants orchestrate survival fate in mice

Matsuo, Tomohiro; Isosaka, Tomoko; Tang, Lijun; Soga, Tomoyoshi; Kobayakawa, Reiko; Kobayakawa, Ko

doi:10.1101/2020.05.17.100933

Cited by 2 publications

(8 citation statements)

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“…We compared the 2MT-induced thermoregulatory response between wild-type and Trpa1 -/mice using a behavior paradigm as previously described 33,35 . To study the effect of 2MT on the change of body temperature, we used infrared (IR) thermography combined with implanted telemetry transmitter to measure in real time the cutaneous and core body temperature, respectively (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Because Sp5 neurons also project to PB 66,67 , we believe that a subpopulation of vGlut2 + PBel neurons receive the 2MT-evoked innate fear signal directly from TG or indirectly via Sp5 neurons. Once activated, these vGlut2 + PBel neurons transmit the signal to Interestingly, Matsuo and colleagues found that chemogenetic activation of the NTS-PB pathway could also induce hypothermia 35 , suggesting the potential existence of a PB-PSTh-NTS-PB feedforward loop for 2MT-evoked hypothermia. Furthermore, they also reported that trigeminal, vagal, or olfactory ablation could partially suppress 2MT-evoked hypothermia 62 .…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we discovered that exposure to 2MT could induce rapid hypothermia accompanied by elevated tail temperature in wild-type mice, but not in Trpa1 -/mice. Based on our current studies (this paper and Kobayakawa's co-submitted paper) 35,62 , we propose a working model for the neural mechanism underlying 2MT-evoked hypothermia (Fig. 8).…”

Section: Discussionmentioning

confidence: 99%

“…The two major autonomic responses to reduce body temperature are the suppression of brown adipose tissue (BAT)-dependent thermogenesis and facilitation of heat dissipation from glabrous skin, such as from the tail in rodents 3 . Matsuo and colleagues recently discovered that 2MT-evoked hypothermia was independent of suppression of BAT thermogenesis 35 . In this study, we found that 2MT exposure induced a sharp (up to 6 ºC) increase in the tail temperature accompanying the rapid reduction in the skin and core body temperature in wild-type mice (Fig.…”

Section: How Does Psth-nts Regulate Tail Vasodilation?mentioning

confidence: 99%

“…On the other hand, potent stress or fear stimuli that threaten the survival of animals, such as long-lasting immobile stress and hypoxia, induces hypothermia 9,[28][29][30] . Moreover, potent innate fear odor 2MT can trigger acute hypothermia accompanying robust defensive behaviors, such as freezing 33,34,35 . Thus, it is plausible that extreme stress or fear stimuli may induce hypothermia to promote animal survival, although the biological significance of stress/fear-evoked hypothermia is unclear.…”

Section: Biological Significance Of Innate Fear-associated Hypothermiamentioning

confidence: 99%

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Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia

Liu

Lee

Asher

et al. 2020

Preprint

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Mammals normally maintain a constant body temperature irrespective of their environmental temperature. However, emotions such as fear can trigger acute changes in body temperature accompanying defensive behaviors to enhance survival in life-threatening conditions. The neural mechanisms of fear-associated thermoregulation remain unclear. Here, we find that innate fear odor 2-methyl-2-thiazoline (2MT) evokes rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1, the chemosensor for 2MT. Following 2MT exposure, wild-type but not Trpa1-/- mice exhibit high c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel), and nucleus of the solitary tract (NTS). Tetanus toxin light chain (TeLC)-mediated inactivation of NTS-projecting PSTh neurons blunts 2MT-evoked hypothermia and abrogated tail temperature increase. Optogenetic activation of the PSTh-rostral NTS (RNTS) pathway specifically induces hypothermia and elevated tail temperature. Moreover, selective opto-stimulation of 2MT-activated PSTh-projecting PBel neurons, by capturing activated neuronal ensembles (CANE), induces hypothermia and elevated tail temperature. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel and PSTh or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail temperature increment. Taken together, these results uncover a novel PBel-PSTh-NTS neural pathway that underlies 2MT-evoked innate fear-associated hypothermia and tail vasodilation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: How Does Psth-nts Regulate Tail Vasodilation?mentioning

confidence: 99%

Section: Biological Significance Of Innate Fear-associated Hypothermiamentioning

confidence: 99%

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Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia

Liu

Lee

Asher

et al. 2020

Preprint

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Effects of 2-Methyl-2-Thiazoline on Circulatory Dynamics and Intestinal Vascular System in Rabbits With Endotoxic Shock

Onoe

Muroya

Nakamura

et al. 2022

Shock

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We hypothesized that circulatory and jejunal mucosal blood flow would improve after 2-methyl-2thiazoline (2MT) administration in endotoxic shock. This study aimed to evaluate changes in systemic circulation and in superior mesenteric venous (SMV) blood flow and jejunal mucosal tissue blood flow of the intestinal vascular system over time after administration of 2MT in rabbits with endotoxic shock. We created four groups (n = 6 each): control group, LPS (1 mg/kg) group, 2MT (80 mg/kg) group, and LPS-2MT group. As indicators of circulation, we measured MAP, heart rate, cardiac index, lactic acid level, SMV blood flow, and jejunal mucosal tissue blood flow every 30 min from 0 to 240 min. The drop in MAP observed in the LPS group was suppressed by 2MT administration. Superior mesenteric venous blood flow dropped temporarily with LPS administration but then rose thereafter. After administration of 2MT to the LPS group, SMV blood flow began to rise earlier than that in the LPS group and did not decline below that of the control group thereafter. In the LPS group, jejunal mucosal tissue blood flow transiently decreased and then increased but at a lower level than that in the control group. However, in the LPS-2MT group, although a transient decrease in jejunal mucosal tissue blood flow was observed, its flow then improved to the level of the control group. An interaction between 2MT and LPS was observed for jejunal mucosal tissue blood flow from 90 to 180 min and at 240 min (P < 0.05). We showed that 2MT maintained MAP and improved SMV blood flow and jejunal mucosal tissue blood flow. In a rabbit model of endotoxic shock, 2MT had a positive effect on MAP and jejunal mucosal tissue blood flow.

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Thiazoline-related TRPA1 agonist odorants orchestrate survival fate in mice

Abstract: TFO-induced strong crisis perception maximizes latent life-protective effects by shifting metabolism to a crisis response mode characterized by hypothermia, hypometabolism and crisis immunity.

Cited by 2 publications

References 86 publications

Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia

Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia

Effects of 2-Methyl-2-Thiazoline on Circulatory Dynamics and Intestinal Vascular System in Rabbits With Endotoxic Shock

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