1,721,027 research outputs found
Hypothermia, torpor and the fundamental importance of understanding the central control of thermoregulation
No full textActivation of central adenosine A1 receptors in the rat, a non-hibernating species, mimics the physiological characteristics of torpor and could thus represent a basis for the development of pharmacological approaches to induce therapeutic hypothermia in pathologies such as brain hemorrhage and ischemia, and to facilitate long-term space travel
Vagal nerve stimulation can elicit both activation and inhibition of brown adipose tissue sympathetic nerve activity (1131.6)
No full textThe dependence of BAT thermogenesis on the availability of metabolic substrates suggests that metabolic signals from the viscera could influence the sympathetic outflow driving BAT thermogenesis. Viscerosensory afferents in the proximal end of the sectioned left cervical vagus nerve were activated with electrical stimulation in anesthetized, ventilated rats while recording the SNA to the contralateral interscapular BAT pad. Paired-pulse VNS delivered once every 5 sec evoked excitatory evoked potentials in BAT SNA with a peak latency of ~ 180 ms, followed by a ~2 s period of quiescent BAT SNA. Within a few seconds of stimulus onset, continuous, single-pulse VNS at 2 Hz produced a complete inhibition of cold-evoked BAT SNA that was sustained for at least 2 hrs of maintained VNS. Similarly, activation of neurons in the intermediate nucleus of the solitary tract (iNTS), at the level of the area postrema, with nanoinjections (60 pmol) of bicuculline also inhibits the VNS-evoked excitation of BAT SNA. Inhibition of neurons in the rostral ventromedial medullary raphe pallidus region also eliminates the VNS-evoked excitation of BAT SNA. These data support the existence of populations of vagal afferents whose stimulation can (1) increase BAT SNA via activation of BAT sympathetic premotor neurons or (2) inhibit BAT SNA via activation of BAT sympathoinhibitory neurons in the iNTS (see Am. J. Physiol. Regul. Integr. Comp. Physiol., 299:R277-R290, 2010. PMC2904145)
Orexin modulates brown adipose tissue thermogenesis
Full text linkNon-shivering thermogenesis in brown adipose tissue (BAT) plays an important role in thermoregulation. In addition, activations of BAT have important implications for energy homeostasis due to the metabolic consumption of energy reserves entailed in the production of heat in this tissue. In this conceptual overview we describe the role of orexins/hypocretins within the central nervous system in the modulation of thermogenesis in BAT under several physiological conditions. Within this framework, we consider potential neural mechanisms underlying the pathological conditions associated with the absence of the central orexinergic modulation of BAT thermogenesis and energy expenditure. Overall, the experimental basis for our understanding of the role of central orexin in regulating body temperature and energy homeostasis provides an illustrative example that highlights several general principles and caveats that should help to guide future investigations of the neurochemical regulation of thermogenesis and metabolism
α2 adrenergic receptor-mediated inhibition of thermogenesis
No full text�2 adrenergic receptor (�2-AR) agonists have been used as antihypertensive agents, in the management of drug withdrawal, and as sedative analgesics. Since �2-AR agonists also influence the regulation of body temperature, we explored their potential as antipyretic agents. This study delineates the central neural substrate for the inhibition of rat brown adipose tissue (BAT) and shivering thermogenesis by �2-AR agonists. Nanoinjection of the �2-AR agonist clonidine (1.2 nmol) into the rostral raphe pallidus area (rRPa) inhibited BAT sympathetic nerve activity (SNA) and BAT thermogenesis. Subsequent nanoinjection of the �2-AR antagonist idazoxan (6 nmol) into the rRPa reversed the clonidine-evoked inhibition of BAT SNA and BAT thermogenesis. Systemic administration of the �2-AR agonists dexmedetomidine (25 �g/kg, i.v.) and clonidine (100 �g/kg, i.v.) inhibited shivering EMGs, BAT SNA, and BAT thermogenesis, effects that were reversed by nanoinjection of idazoxan (6 nmol) into the rRPa. Dexmedetomidine (100 �g/kg, i.p.) prevented and reversed lipopolysaccharide-evoked (10 �g/kg, i.p.) thermogenesis in free-behaving rats. Cholera toxin subunit b retrograde tracing from rRPa and pseudorabies virus transynaptic retrograde tracing from BAT combined with immunohistochemistry for catecholaminergic biosynthetic enzymes revealed the ventrolateral medulla as the source of catecholaminergic input to the rRPa and demonstrated that these catecholaminergic neurons are synaptically connected to BAT. Photostimulation of ventrolateral medulla neurons expressing the PRSx8- ChR2-mCherry lentiviral vector inhibited BAT SNA via activation of 2-ARs in the rRPa. These results indicate a potent inhibition of BAT and shivering thermogenesis by �2-AR activation in the rRPa, and suggest a therapeutic potential of �2-AR agonists for reducing potentially lethal elevations in body temperature during excessive fever. � 2013 the authors
Adenosine A1-receptor agonist (CHA) produces a hypothermic state by reducing bat thermogenesis
No full textCentral activation of the A1 adenosine receptor (A1AR) induces a hypothermic, torpor-like state in the rat
No full textSince central activation of A1 adenosine receptors (A1ARs) plays an important role in the induction of the hypothermic and hypometabolic torpid state in hibernating mammals, we investigated the potential for the A1AR agonist N6-cyclohexyladenosine to induce a hypothermic, torpor-like state in the (nonhibernating) rat. Core and brown adipose tissue temperatures, EEG, heart rate, and arterial pressure were recorded in free-behaving rats, and c-fos expression in the brain was analyzed, following central administration of N6-cyclohexyladenosine. Additionally, we recorded the sympathetic nerve activity to brown adipose tissue; expiratory CO2 and skin, core, and brown adipose tissue temperatures; and shivering EMGs in anesthetized rats following central and localized, nucleus of the solitary tract, administration of N6-cyclohexyladenosine. In rats exposed to a cool (15�C) ambient temperature, central A1AR stimulation produced a torpor-like state similar to that in hibernating species and characterized by a marked fall in body temperature due to an inhibition of brown adipose tissue and shivering thermogenesis that is mediated by neurons in the nucleus of the solitary tract. During the induced hypothermia, EEG amplitude and heart rate were markedly reduced. Skipped heartbeats and transient bradycardias occurring during the hypothermia were vagally mediated since they were eliminated by systemic muscarinic receptor blockade. These findings demonstrate that a deeply hypothermic, torpor-like state can be pharmacologically induced in a nonhibernating mammal and that recovery of normothermic homeostasis ensues upon rewarming. These results support the potential for central activation of A1ARs to be used in the induction of a hypothermic, therapeutically beneficial state in humans. � 2013 the authors
An orexinergic projection from perifornical hypothalamus to raphe pallidus increases rat brown adipose tissue thermogenesis
No full textNon-shivering thermogenesis in brown adipose tissue (BAT) plays an important role in thermoregulatory cold-defense and, through its metabolic consumption of energy reserves to produce heat, can affect the long-term regulation of adiposity. An orexinergic pathway from the perifornical lateral hypothalamus (PeF/LH) to the rostral raphe pallidus (rRPa) has been demonstrated to increase the gain of the excitatory drives to medullary sympathetic premotor neurons controlling BAT sympathetic outflow and BAT thermogenesis. With this background, we consider neural mechanisms that could underlie orexin's modulation of the excitability of BAT sympathetic premotor neurons in rRPa and the potential role of altered BAT thermogenesis in pathological conditions associated with the absence of the central orexin system. Overall, these new data enhance our understanding of the role of central orexin in regulating body temperature and energy homeostasis and provide further insight into the neurochemical regulation of BAT thermogenesis and metabolism
REM Sleep and Endothermy: Potential Sites and Mechanism of a Reciprocal Interference
Full text linkNumerous data show a reciprocal interaction between REM sleep and thermoregulation. During REM sleep, the function of thermoregulation appears to be impaired; from the other hand, the tonic activation of thermogenesis, such as during cold exposure, suppresses REM sleep occurrence. Recently, both the central neural network controlling REM sleep and the central neural network controlling thermoregulation have been progressively unraveled. Thermoregulation was shown to be controlled by a central "core" circuit, responsible for the maintenance of body temperature, modulated by a set of accessory areas. REM sleep was suggested to be controlled by a group of hypothalamic neurons overlooking at the REM sleep generating circuits within the brainstem. The two networks overlap in a few areas, and in this review, we will suggest that in such overlap may reside the explanation of the reciprocal interaction between REM sleep and thermoregulation. Considering the peculiar modulation of thermoregulation by REM sleep the result of their coincidental evolution, REM sleep may therefore be seen as a period of transient heterothermy
Hibernation, hypothermia and a possible therapeutic "shifted homeostasis" induced by central activation of a1 adenosine receptor (A1AR)
No full textThe positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Pharmacological manipulation of central autonomic thermoregulatory circuits could represent a potential target for the induction of a hypothermic state. Here we present a brief description of the CNS thermoregulatory centers and how the manipulation of these circuits can be useful in the treatment of pathological conditions such as stroke or brain hemorrhage
Thermoregulatory Inversion - a novel thermoregulatory paradigm
No full textTo maintain core body temperature in mammals, the normal 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 non-hibernating/torpid species, exhibit a "Thermoregulatory Inversion", 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 pharmacologic mechanism through which a deeply hypothermic state can be achieved in non-hibernating/torpid mammals, possibly including humans
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