Thermoregulatory inversion: a novel thermoregulatory paradigm.
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.
Department of Neurological Surgery, Oregon Health and Science University, Portland, Oregon; and domenico.tupone@gmail.com.
Domenico
0000-0002-4238-1011
D
Tupone
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania.
Georgina
G
Cano
Department of Neurological Surgery, Oregon Health and Science University, Portland, Oregon; and.
Shaun F
SF
Morrison
D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D004302:Dorsomedial Hypothalamic Nucleus / Q000502:physiology*; D025461:Feedback, Physiological / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D017694:Rewarming / Q000379:methods; D012867:Skin / Q000294:innervation; D012879:Skin Physiological Phenomena; D013564:Sympathetic Nervous System / Q000502:physiology
D043682:Receptor, Adenosine A1
brown adipose tissue; hibernation; hypothermia; thermogenesis; thermoregulation