The dorsomedial hypothalamus: a new player in thermoregulation

2007 ◽  
Vol 292 (1) ◽  
pp. R47-R63 ◽  
Author(s):  
Joseph A. DiMicco ◽  
Dmitry V. Zaretsky
Keyword(s):  
Sympathetic Nerve Activity ◽  
Core Body Temperature ◽  
Central Administration ◽  
Dorsomedial Hypothalamus ◽  
Brown Adipose ◽  
Significant Difference ◽  
Raphe Pallidus ◽  
Core Body ◽  
The Brain ◽  
Cutaneous Vasoconstriction

Neurons in the dorsomedial hypothalamus (DMH) play key roles in physiological responses to exteroceptive (“emotional”) stress in rats, including tachycardia. Tachycardia evoked from the DMH or seen in experimental stress in rats is blocked by microinjection of the GABAA receptor agonist muscimol into the rostral raphe pallidus (rRP), an important thermoregulatory site in the brain stem, where disinhibition elicits sympathetically mediated activation of brown adipose tissue (BAT) and cutaneous vasoconstriction in the tail. Disinhibition of neurons in the DMH also elevates core temperature in conscious rats and sympathetic activity to least significant difference interscapular BAT (IBAT) and IBAT temperature in anesthetized preparations. The latter effects are blocked by microinjection of muscimol into the rRP, while microinjection of muscimol into either the rRP or DMH suppresses increases in sympathetic nerve activity to IBAT, IBAT temperature, and core body temperature elicited either by microinjection of PGE2 into the preoptic area (an experimental model for fever), or central administration of fentanyl. Neurons concentrated in the dorsal region of the DMH project directly to the rRP, a location corresponding to that of neurons transsynaptically labeled from IBAT. Thus these neurons control nonshivering thermogenesis in rats, and their activation signals its recruitment in diverse experimental paradigms. Evidence also points to a role for neurons in the DMH in thermoregulatory cutaneous vasoconstriction, shivering, and endocrine adjustments. These directions provide intriguing avenues for future exploration that may expand our understanding of the DMH as an important hypothalamic site for the integration of autonomic, endocrine, and behavioral responses to diverse challenges.

scholarly journals Thermoregulatory inversion: a novel thermoregulatory paradigm

2017 ◽  
Vol 312 (5) ◽  
pp. R779-R786 ◽  
Author(s):  
Domenico Tupone ◽  
Georgina Cano ◽  
Shaun F. Morrison
Keyword(s):  
Body Temperature ◽  
Core Temperature ◽  
Neural Circuit ◽  
Core Body Temperature ◽  
Normal Body Temperature ◽  
Dorsomedial Hypothalamus ◽  
Pharmacological Mechanism ◽  
Brown Adipose ◽  
Skin Cooling ◽  
Core Body

To maintain core body temperature in mammals, the normal central nervous system (CNS) thermoregulatory reflex networks produce an increase in brown adipose tissue (BAT) thermogenesis in response to skin cooling and an inhibition of the sympathetic outflow to BAT during skin rewarming. In contrast, these normal thermoregulatory reflexes appear to be inverted in hibernation/torpor; thermogenesis is inhibited during exposure to a cold environment, allowing dramatic reductions in core temperature and metabolism, and thermogenesis is activated during skin rewarming, contributing to a return of normal body temperature. Here, we describe two unrelated experimental paradigms in which rats, a nonhibernating/torpid species, exhibit a “thermoregulatory inversion,” which is characterized by an inhibition of BAT thermogenesis in response to skin cooling, and a switch in the gain of the skin cooling reflex transfer function from negative to positive values. Either transection of the neuraxis immediately rostral to the dorsomedial hypothalamus in anesthetized rats or activation of A1 adenosine receptors within the CNS of free-behaving rats produces a state of thermoregulatory inversion in which skin cooling inhibits BAT thermogenesis, leading to hypothermia, and skin warming activates BAT, supporting an increase in core temperature. These results reflect the existence of a novel neural circuit that mediates inverted thermoregulatory reflexes and suggests a pharmacological mechanism through which a deeply hypothermic state can be achieved in nonhibernating/torpid mammals, possibly including humans.

scholarly journals Contribution of nucleus raphe magnus to thermoregulation

2020 ◽  
Vol 24 (3) ◽  
pp. 165-173
Author(s):  
Masoumeh Kourosh Arami ◽  
◽  
Alireza Komaki ◽  
Shahriar Gharibzadeh ◽  
◽  
...  
Keyword(s):  
Body Temperature ◽  
Energy Homeostasis ◽  
Core Body Temperature ◽  
Nucleus Raphe Magnus ◽  
Brown Adipose ◽  
Raphe Magnus ◽  
Blood Flow Control ◽  
Core Body ◽  
Homeostatic Response ◽  
Cutaneous Vasoconstriction

Thermoregulation is the maintenance of the core body temperature. The regulation of body temperature is one of the most important functions of the nervous system. Nucleus raphe magnus, as a central circuit coordinates the homeostatic response and maintains body temperature during environmental temperature challenges and adjusts body temperature during the inflammatory response and behavioral states and in response to decreasing energy homeostasis. Our aim in this review is the understanding of thermoregulation by raphe magnus in mammals. This review summarizes the basic concepts of thermoregulation and subsequently assesses the physiological responses to cold stress, including skin blood flow control, sweating, sympathetic-derived cutaneous vasoconstriction and peripheral thermoregulatory control in brown adipose tissue.

scholarly journals Glycinergic inhibition of BAT sympathetic premotor neurons in rostral raphe pallidus

2017 ◽  
Vol 312 (6) ◽  
pp. R919-R926 ◽  
Author(s):  
Ellen Paula Santos da Conceição ◽  
Christopher J. Madden ◽  
Shaun F. Morrison
Keyword(s):  
Core Body Temperature ◽  
Cardiovascular Parameters ◽  
Potent Inhibition ◽  
Brown Adipose ◽  
Premotor Neurons ◽  
Sympathetic Premotor Neurons ◽  
Glycinergic Inhibition ◽  
Raphe Pallidus ◽  
Core Body ◽  
Inhibitory Regulation

The rostral raphe pallidus (rRPa) contains sympathetic premotor neurons controlling thermogenesis in brown adipose tissue (BAT). We sought to determine whether a tonic activation of glycineA receptors (GlyAR) in the rRPa contributes to the inhibitory regulation of BAT sympathetic nerve activity (SNA) and of cardiovascular parameters in anesthetized rats. Nanoinjection of the GlyAR antagonist, strychnine (STR), into the rRPa of intact rats increased BAT SNA (peak: +495%), BAT temperature (TBAT, +1.1°C), expired CO2, (+0.4%), core body temperature (TCORE, +0.2°C), mean arterial pressure (MAP, +4 mmHg), and heart rate (HR, +57 beats/min). STR into rRPa in rats with a postdorsomedial hypothalamus transection produced similar increases in BAT thermogenic and cardiovascular parameters. Glycine nanoinjection into the rRPa evoked a potent inhibition of the cooling-evoked increases in BAT SNA (nadir: −74%), TBAT (−0.2°C), TCORE (−0.2°C), expired CO2 (−0.2%), MAP (−8 mmHg), and HR (−22 beats/min) but had no effect on the increases in these variables evoked by STR nanoinjection into rRPa. Nanoinjection of GABA into the rRPa inhibited the STR-evoked BAT SNA (nadir: −86%) and reduced the expired CO2 (−0.4%). Blockade of glutamate receptors in rRPa reduced the STR-evoked increases in BAT SNA (nadir: −61%), TBAT (−0.5°C), expired CO2 (−0.3%), MAP (−9 mmHg), and HR (−33 beats/min). We conclude that a tonically active glycinergic input to the rRPa contributes to the inhibitory regulation of the discharge of BAT sympathetic premotor neurons and of BAT thermogenesis and energy expenditure.

scholarly journals A refined method to monitor arousal from hibernation in the European hamster

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Fredrik A. F. Markussen ◽  
Vebjørn J. Melum ◽  
Béatrice Bothorel ◽  
David G. Hazlerigg ◽  
Valérie Simonneaux ◽  
...  
Keyword(s):  
Body Temperature ◽  
Core Body Temperature ◽  
Behavioural Adaptation ◽  
Ventilation Frequency ◽  
Reduced Body ◽  
Brown Adipose ◽  
Invasive Method ◽  
Warming Rate ◽  
Core Body ◽  
Environmental Temperatures

Abstract Background Hibernation is a physiological and behavioural adaptation that permits survival during periods of reduced food availability and extreme environmental temperatures. This is achieved through cycles of metabolic depression and reduced body temperature (torpor) and rewarming (arousal). Rewarming from torpor is achieved through the activation of brown adipose tissue (BAT) associated with a rapid increase in ventilation frequency. Here, we studied the rate of rewarming in the European hamster (Cricetus cricetus) by measuring both BAT temperature, core body temperature and ventilation frequency. Results Temperature was monitored in parallel in the BAT (IPTT tags) and peritoneal cavity (iButtons) during hibernation torpor-arousal cycling. We found that increases in brown fat temperature preceded core body temperature rises by approximately 48 min, with a maximum re-warming rate of 20.9℃*h-1. Re-warming was accompanied by a significant increase in ventilation frequency. The rate of rewarming was slowed by the presence of a spontaneous thoracic mass in one of our animals. Core body temperature re-warming was reduced by 6.2℃*h-1 and BAT rewarming by 12℃*h-1. Ventilation frequency was increased by 77% during re-warming in the affected animal compared to a healthy animal. Inspection of the position and size of the mass indicated it was obstructing the lungs and heart. Conclusions We have used a minimally invasive method to monitor BAT temperature during arousal from hibernation illustrating BAT re-warming significantly precedes core body temperature re-warming, informing future study design on arousal from hibernation. We also showed compromised re-warming from hibernation in an animal with a mass obstructing the lungs and heart, likely leading to inefficient ventilation and circulation.

The contribution of the vagus nerve in interleukin-1β-induced fever is dependent on dose

2001 ◽  
Vol 280 (4) ◽  
pp. R929-R934 ◽  
Author(s):  
Michael K. Hansen ◽  
Kevin A. O'Connor ◽  
Lisa E. Goehler ◽  
Linda R. Watkins ◽  
Steven F. Maier
Keyword(s):  
Core Body Temperature ◽  
Vagal Afferents ◽  
Interleukin 1Β ◽  
Blood Levels ◽  
Low Doses ◽  
Neural Pathway ◽  
Subdiaphragmatic Vagotomy ◽  
Core Body ◽  
Neural Signaling ◽  
The Brain

It has been suggested that proinflammatory cytokines communicate to the brain via a neural pathway involving activation of vagal afferents by interleukin-1β (IL-1β), in addition to blood-borne routes. In support, subdiaphragmatic vagotomy blocks IL-1β-induced, brain-mediated responses such as fever. However, vagotomy has also been reported to be ineffective. Neural signaling would be expected to be especially important at low doses of cytokine, when local actions could occur, but only very small quantities of cytokine would become systemic. Here, we examined core body temperature after intraperitoneal injections of three doses of recombinat human IL-1β (rh-IL-1β). Subdiaphragmatic vagotomy completely blocked the fever produced by 0.1 μg/kg, only partially blocked the fever produced by 0.5 μg/kg, and had no effect at all on the fever that followed 1.0 μg/kg rh-IL-1β. Blood levels of rh-IL-1β did not become greater than normal basal levels of endogenous rat IL-β until the 0.5-μg/kg dose nor was IL-1β induced in the pituitary until this dose. These results suggest that low doses of intraperitoneal IL-1β induce fever via a vagal route and that dose may account for some of the discrepancies in the literature.

scholarly journals Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction

2017 ◽  
Vol 114 (36) ◽  
pp. 9731-9736 ◽  
Author(s):  
Rigo Cintron-Colon ◽  
Manuel Sanchez-Alavez ◽  
William Nguyen ◽  
Simone Mori ◽  
Ruben Gonzalez-Rivera ◽  
...  
Keyword(s):  
Growth Factor ◽  
Body Temperature ◽  
Calorie Restriction ◽  
Core Body Temperature ◽  
Insulin Like Growth Factor ◽  
Hypothalamic Nuclei ◽  
The Central Nervous System ◽  
Temperature Homeostasis ◽  
Core Body ◽  
The Brain

When food resources are scarce, endothermic animals can lower core body temperature (Tb). This phenomenon is believed to be part of an adaptive mechanism that may have evolved to conserve energy until more food becomes available. Here, we found in the mouse that the insulin-like growth factor 1 receptor (IGF-1R) controls this response in the central nervous system. Pharmacological or genetic inhibition of IGF-1R enhanced the reduction of temperature and of energy expenditure during calorie restriction. Full blockade of IGF-1R affected female and male mice similarly. In contrast, genetic IGF-1R dosage was effective only in females, where it also induced transient and estrus-specific hypothermia in animals fed ad libitum. These effects were regulated in the brain, as only central, not peripheral, pharmacological activation of IGF-1R prevented hypothermia during calorie restriction. Targeted IGF-1R knockout selectively in forebrain neurons revealed that IGF signaling also modulates calorie restriction-dependent Tbregulation in regions rostral of the canonical hypothalamic nuclei involved in controlling body temperature. In aggregate, these data identify central IGF-1R as a mediator of the integration of nutrient and temperature homeostasis. They also show that calorie restriction, IGF-1R signaling, and body temperature, three of the main regulators of metabolism, aging, and longevity, are components of the same pathway.

scholarly journals Comparison of Tympanic and Tail Temperatures in Angus and Brahman Steers

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Dikmen S ◽  
Davila KMS ◽  
Rodriquez E ◽  
Scheffler TL ◽  
Oltenacu PA ◽  
...  
Keyword(s):  
Body Temperature ◽  
Repeated Measures ◽  
Core Body Temperature ◽  
The Body ◽  
Tympanic Temperature ◽  
Repeated Measure ◽  
Important Indicator ◽  
Significant Difference ◽  
Brahman Steers ◽  
Core Body

In cattle, core body temperature can be used as an important indicator of heat stress level. However, accurately recording core body temperature can be difficult and labor intensive. The objectives of the current study were 1) to compare the recorded tympanic and tail body temperature measurements in steers and 2) to determine the body temperature change of Angus and Brahman steers in a hot and humid environment. Data was analyzed using a repeated measure model where repeated measures were hourly tympanic and tail temperatures and their difference for individual steers during the day of the experiment. There was a significant breed effect (P=0.01), hour (P<0.0001) and breed by hour interaction (P<0.0001) for the tympanic temperature. Brahman steers, which are known to have superior thermotolerance, maintained a lower body temperature than the Angus steers during the afternoon under grazing conditions. In the Brahman steers there was only a minimal increase in the body temperature throughout the day, an evidence of the thermotolerance ability of the breed. In the Angus steers, which experienced an increase in their body temperature from hour to hour with a peak around 1600 hour; there was a significant difference between the tympanic and tail temperature during the times when the body temperature as measured by the tympanic recordings was the highest (1300 to 1700 hour). Our results indicate that the tympanic temperature can be used to accurately and continuously monitor core body temperature in a natural environment for up to several days and without disturbing the animal.

scholarly journals Impaired Thermogenesis and a Molecular Signature for Brown Adipose Tissue inId2Null Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Zhou ◽  
Maricela Robles-Murguia ◽  
Deepa Mathew ◽  
Giles E. Duffield
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Core Body Temperature ◽  
Specific Pattern ◽  
Molecular Signature ◽  
Brown Adipose ◽  
Core Body ◽  
The Impact

Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated thatId2null mice have sex-specific elevated glucose uptake in brown adipose tissue (BAT). Here we further explored the role ofId2in the regulation of core body temperature over the circadian cycle and the impact ofId2deficiency on genes involved in insulin signaling and adipogenesis in BAT. We discovered a reduced core body temperature inId2−/− mice. Moreover, inId2−/− BAT, 30 genes includingIrs1,PPARs, andPGC-1s were identified as differentially expressed in a sex-specific pattern. These data provide valuable insights into the impact ofId2deficiency on energy homeostasis of mice in a sex-specific manner.

scholarly journals Regulatory effects of brown adipose tissue thermogenesis on maternal metabolic adaptation, placental efficiency, and fetal growth in mice

2018 ◽  
Vol 315 (6) ◽  
pp. E1224-E1231 ◽  
Author(s):  
Liping Qiao ◽  
Samuel Lee ◽  
Amanda Nguyen ◽  
William W. Hay ◽  
Jianhua Shao
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Brown Adipose Tissue ◽  
Fetal Growth ◽  
Core Body Temperature ◽  
Metabolic Adaptation ◽  
Glucose Transporter 1 ◽  
Brown Adipose ◽  
Placental Efficiency ◽  
Core Body

To determine the role of UCP1-mediated thermogenesis in controlling maternal metabolic adaptation to pregnancy, energy metabolism of C57BL/6 wild-type (WT) and Ucp1 gene knockout ( Ucp1−/−) mice was studied during pregnancy. With the progression of pregnancy, maternal energy expenditure rates (EERs), expression of UCP1, and core body temperature steadily declined in WT dams. Despite no significant alterations in core body temperature and weight gain during pregnancy, Ucp1−/− dams exhibited lower rates in EER decline. High-fat (HF) feeding not only robustly increased maternal UCP1 expression and core body temperature but also abolished gestation-suppressed EER in WT dams. However, HF-increased EERs were significantly attenuated in Ucp1−/− dams. Significantly increased fetal body weights and fetal/placental weight ratio were detected in fetuses from Ucp1−/− dams compared with fetuses from WT dams. Markedly increased expression levels of glucose transporter 1 and amino acid transporters were also observed in placentas from Ucp1−/− dams. Furthermore, blood glucose concentrations of fetuses from Ucp1−/− dams were significantly higher than those of fetuses from WT dams, indicating that maternal UCP1 has an inhibitory effect on placental efficiency and fetal growth. Taken all together, this study demonstrated that maternal brown adipose tissue plays an important role in controlling maternal metabolic adaptation and placental nutrient transport.

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