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Nitric oxide regulates body temperature, neuronal activation and interleukin-1 beta gene expression in the hypothalamic paraventricular nucleus in response to immune stress.

An immune challenge initiates a complex cascade of events in the body including important responses from the central nervous system. As nitric oxide (NO) has been implicated in the central regulation of neuroendocrine and autonomic responses, this study was performed to determine if NO regulates physiological responses, neuronal activation, and/or interleukin-1 beta (IL-1 beta) gene expression in the paraventricular nucleus of the rat hypothalamus (PVN) in response to intravenous endotoxin, lipopolysaccharide (LPS, 100 microg/kg). Intracerebroventricular injections of NO synthase (NOS) inhibitors (7-nitroindazole sodium salt for neuronal NOS, N(G)-nitro-L-arginine for neuronal NOS and endothelial NOS, and aminoguanidine for inducible NOS) in LPS-treated rats showed that inhibition of NOS eliminated the drop in body temperature and led to increased neuronal activation in the PVN as assessed by immunohistochemistry for Fos-like immunoreactivity. Activation of NO-producing PVN neurons was also increased in these rats suggesting that NO influences neuronal NOS activity in PVN neurons. Finally, increased IL-1 beta gene expression in the PVN of LPS-treated rats receiving N(G)-nitro-L-arginine showed that NO regulates brain IL-1 beta gene expression. The results obtained with the NOS inhibitors support the hypothesis that NO produced from eNOS in the brain participates in temperature regulation, and inhibits PVN neuronal activity and IL-1 beta gene expression during immune stress.

Animals↗

Body temperature regulation in the rat.

In loosely-restrained adult conscious rats exposed to stepwise changes in ambient temperature (T(a)) from 25 to 5 degrees C or from 20 to 35 degrees C, we have recorded body and tail temperatures, metabolic rate (VO(2)), shivering and ventilation (V). It was found that VO(2) and V vary with T(a) and show a nadir for a T(a) of 30 degrees C whereas shivering starts at 20 degrees C and increases progressively with cold exposure. T(tail) follows changes in T(a) whereas T(body) decreases slightly in cold and increases markedly in warm exposure. These results suggest that the control of T(body) interacts with the control of breathing in order to increase VO(2) during cold exposure and to facilitate evaporative respiratory heat dissipation during warm exposure.

Journal Article↗

Role of afferent pathways of heat and cold in body temperature regulation.

The detection of surface and internal temperatures is achieved by axons terminating at lamina I of the spinal dorsal horn, otherwise approached only by nociceptive afferents. Recent advances in thermal physiology research have disclosed that temperature-sensitive ion channels belonging to the "transient receptor potential" family exist in the peripheral sensory neurons and in the brain. Thermosensory, nociceptive and polymodal afferents project to different thalamic nuclei, and specific pathways to the insular cortex evoke the conscious experience of thermal sensation. The posterior insular region represents discriminative thermal sensation, while the largest correlation with subjective ratings of temperature is located in the orbitofrontal and anterior insular cortex. The insular cortex forms an integrative part of the limbic system and is closely tied with the hypothalamus, the amygdala, the anterior cingulate cortex and the orbitofrontal cortex and emerges as the main coordinator of behavioral, autonomic and endocrine responses to both non-noxious and noxious thermal stimuli. The firing rate of warm and cold receptors is not altered by pyrogens. A strong correlation between the onset of fever and production of superoxide by macrophages following the injection of pyrogens implicates reactive oxygen species as elicitors of fever, a hypothesis strengthened by the observation that oxygen radical scavengers or thiol reductants act as antipyretics. Oxidative stress appears to be sensed by the brain and a likely structure for its detection may be the redox-sensitive site of the N-methyl-D-aspartate (NMDA) receptor for glutamate, in that oxidation of this site causes fever while its reduction lowers body temperature, effects which are abrogated by specific NMDA receptor blockers.

Animals↗

Radiotelemetric measurement of body temperature in feedlot steers during winter.

Little is known concerning body temperature regulation in cattle under conditions of low ambient temperature. To investigate the influence of cold on body temperature regulation, core body temperatures of feedlot steers (crossbred Bos taurus) were monitored for two winters in Nebraska, from late December to mid-March in yr 1 and from late December through June in yr 2. In yr 1, radiotransmitters to monitor temperature were implanted in the peritoneum of five steers (360 kg); in yr 2, four steers (320 kg) were used. Body temperatures and ambient temperatures were recorded at 3-min intervals and were mathematically filtered to produce 120 readings/d. For yr 1 and 2, daily maximum (40.09 and 39.66 degrees C), minimum (38.78 and 38.64 degrees C), and average (39.29 and 39.06 degrees C) body temperatures were not affected by ambient temperatures. Body temperatures exhibited circadian rhythms with the minima at approximately 0800 and the maxima at approximately 1900. For both years, sharp peaks in body temperature were often seen in the evening and, for yr 2, to a lesser extent in the morning. The occurrence of peaks was normally congruent, within a 1.5-h window, across steers. Congruent peaks in the evening with peak heights of 1.05 and .77 degrees C occurred on 65 and 56% of the days in yr 1 and 2, respectively. Occurrence of congruent peaks was correlated with dusk; peaks followed dusk by 30 to 60 min. Ambient temperature also influenced the occurrence of peaks; few peaks were observed when average daily ambient temperatures were below -7.5 degrees C. The dynamic changes in body temperature throughout the day, including the peaks in body temperature after dusk, strongly suggest that thermoregulatory systems in steers respond not only to current ambient conditions, but also to more integrative measures such as day length and daily heat load.

Animals↗

Interaction between veralipride and the endogenous opioid system in the regulation of body temperature in postmenopausal women.

The influence of endogenous opioid peptides on body thermoregulation has been studied in untreated postmenopausal women and in the same subjects after chronic administration of the antidopaminergic drug veralipride (200 mg/day for 20 days). Subjects randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or saline on two consecutive days, both before and after veralipride treatment. In untreated subjects body core temperature, as evaluated by rectal temperature, did not vary during saline infusion, whereas a significant decrease was observed during naloxone infusion. Chronic administration of veralipride significantly increased the hypothermic response to naloxone. Therefore, veralipride seems to increase the activity of endogenous opioid peptides on mechanisms which regulate body temperature in postmenopausal women.

Body Temperature↗

Central nervous regulation of body temperature in vertebrates: comparative aspects.

Thermal fluctuations affect, and are responded to by, nearly all forms of life. The basic vertebrate template has guided and shaped the ways that animals in this subphylum cope with thermal challenges. This has led to a situation where there are major similarities in the neuronal mechanisms which sense temperature and control the responses to temperature change in all vertebrates, from fish to mammals. The PO/AH is the most important single integration site for temperature regulation and (except for birds) is also important in the sensing of core temperature. Other portions of the brainstem as well as the spinal cord are also involved in thermal control and can sense, integrate, and produce appropriate efferent signals to varying degrees. Peripheral thermal input to the hypothalamic areas is via the brainstem reticular areas. A number of studies has related the thermal response characteristics of CNS single neurons to the thermoregulatory output of intact animals. These studies have been performed on neurons in whole animal, brain slice, and tissue culture preparation. These neurophysiological studies of central neurons are informative, but are sometimes difficult to interpret because of the chronic lack of definite criteria to differentiate generalized thermal sensitivity from thermal sensitivity utilized for regulating body temperature. Recent neuroanatomical work has illustrated that many areas previously implicated in the thermoregulatory network (such as the septum, various hypothalamic nuclei, the midbrain reticular formation, and the midbrain raphé nuclei) receive direct projections from PO/AH neurons. When compared, the neurophysiological and neuroanatomical characteristics of the preoptic nucleus and anterior hypothalamic area are similar, but not identical. The broad differences in the responses that vertebrates utilize to deal with thermal change is largely determined by the respiratory medium (water or air) and whether metabolic energy (endothermy) or ambient temperature (ectothermy) is of primary importance in the determination of internal temperature. A number of physiological systems are perturbed in water breathing ectotherms when the ambient temperature is altered. In these vertebrates long-term acclimation is very important and has a major effect on temperature selection. Air breathing ectotherms are less adversely affected by temperature change; long-term thermal acclimation is less important and has little effect upon temperature selection; large thermal changes are often initiated by these animals. Endotherms rely on insulation and a high, variable metabolic rate to maintain a constant internal temperature.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphibians↗

Influence of exercise training and age on uncoupling protein mRNA expression in brown adipose tissue.

The ability to regulate body temperature diminishes with age. Exercise training is known to increase cardiovascular performance, and there is some evidence of a cross-adaptation between exercise and cold tolerance in young rats. The present study was designed to examine the effects of physical training by treadmill running on the capacity for brown adipose tissue (BAT) thermogenesis in young and old rats. To this end, we assessed BAT uncoupling protein (UCP) mRNA expression in sedentary and exercise-trained 5- and 25-mo-old F-344 rats. The amount of UCP mRNA, whether expressed as per unit RNA or per BAT, did not change with either age or training. These data indicate that there is no cross-adaptation by exercise on adaptive thermogenesis in BAT in either young or old rats.

Adipose Tissue, Brown↗

Leptin concentrations in periparturient ewes and their subsequent offspring.

Leptin is an adipocyte-derived hormone that suppresses feed intake and increases energy expenditure. Leptin is also involved in regulating body temperature. Thus, the presence of leptin in milk, which can be absorbed through the gut of neonates immediately after birth, may aid in the survival of neonates born in cold weather. Our objectives were to determine the temporal relationship between concentrations of leptin in postpartum ewe blood serum and ewe milk serum, and to determine whether ewe blood and milk serum leptin concentrations were correlated with concentrations of leptin in lamb blood serum in their off-spring. Approximately 1 wk before the expected date of lambing, blood samples, weights, and body condition scores (BCS; 0 to 5 scale) were collected from 27 mixed-parity ewes. Following parturition, ewe blood and milk samples were collected within 2 h of parturition (d 0), 12 h (d 0.5) and 24 h (d 1) after parturition, again on d 5, and weekly thereafter until d 47. Lambs were blood-sampled and weighed within 2 h of parturition (d 0), bled daily until d 5, and bled and weighed weekly thereafter to d 47. Prior to lambing, ewe blood serum leptin was positively correlated with congruent BCS (r2 = 0, 10, P = 0.06), but not weight (P = 0.14). Following parturition, ewe blood serum leptin was positively correlated with BCS, weight, and milk serum leptin (r2 = 0.14, P < 0.0001, r2 = 0.12, P < 0.0001, and r2 = 0.028, P = 0.04). Leptin in milk serum was correlated with ewe weight (r2=0.05, P = 0.007) but not ewe BCS (P = 0.7); however, concentrations of leptin in both ewe blood and milk serum varied with day of lactation (P = 0.0001), being maximal within 24 h of parturition and declining to nadir concentrations by d 5. Leptin in lamb serum was correlated with milk serum leptin, (r2 = -0.05; P = 0.001), but not ewe blood serum leptin (P = 0.5). Concentrations of leptin in lamb serum increased from birth to d 5 and declined thereafter to nadir concentrations by d 19. Elevated concentrations of leptin in milk during the early stages of lactation may provide a mechanism for thermoregulation, satiation, and homeostatic endocrine control in the neonate.

Animals↗

Evidence for specific involvement of dopamine D1 and D2 receptors in the regulation of body temperature in the rat.

Administration of the selective dopamine D1 and D2 receptor agonists, A 68930 (0.9-60.0 mumol kg-1 s.c.) and quinpirole (0.1-6.0 mumol kg-1 s.c.), produced a dose-dependent decrease in core temperature in the rat. The hypothermia induced by quinpirole (1.5 mumol kg-1) was antagonized by pretreatment with the selective dopamine D2 receptor antagonist, raclopride (1.6 mumol kg-1 s.c.), but not by the dopamine D1 receptor antagonist, SCH 23390 (0.3 mumol kg-1 s.c.), whereas the hypothermia induced by A 68930 (3.8 mumol kg-1) was antagonized by SCH 23390 (0.3 mumol kg-1), but not by raclopride (1.6 mumol kg-1). Together, these results suggest that both dopamine D1 and D2 receptors are specifically involved in the regulation of body temperature in the rat.

Animals↗

Thyroid regulation of body temperature in anaesthetized chickens.

1. Anaesthesia caused marked decreases in the plasma concentrations of triiodothyronine (T3) and thyroxine (T4) and in the body temperature of young fowl. 2. Exogenous T4 or a thyroid hormone secretagogue (somatostatin antiserum), increased endogenous T3 and T4 concentrations and body temperature in conscious birds and prevented the body temperature decline in anaesthetized fowl. 3. These results provide further evidence for a role of T3 and T4 in temperature regulation in birds, particularly during anaesthesia.

Anesthesia↗

cAMP in temperature- and ADH-regulating centers after thermal stress.

cAMP concentrations in temperature-regulating sites of the brain and plasma osmolality were measured after exposure of male rats to 36 degrees C and 37-42% rh. for 10, 20, or 30 min. Plasma osmolality was affected by none of the heat exposures. In both the preoptic area and the posterior medial hypothalamus, cAMP concentrations were increased compared to controls, after 10, 20 and 30 min of heat exposure. In the supraoptic-paraventricular nuclei, neither 10 nor 20 min of exposure resulted in augmented cAMP concentrations; but after 30 min of heat exposure, cAMP levels in these nuclei were significantly greater than in controls. Neurohypophysial cAMP concentrations were increased after both 10 and 30 min of exposure. Cerebral cortical cAMP concentrations were not affected by thermal stress. It is concluded that cAMP is involved in the neural mechanisms which are brought into play to regulate body temperature during acute heat exposure. The significance of this involvement and its relation to the overall temperature-regulating mechanisms of the body are discussed.

Animals↗

Effect of cutaneous denervation of face and trunk on thermoregulatory responses to cold in rats.

The effect of eliminating afferent input from cutaneous thermoreceptors of the face and trunk on the ability of rats to regulate body temperature in cool environments was studied. Thermoregulatory ability in a cool environment was assessed first in a 25 degrees C environment and then during slow (20 min) and rapid (5 min) reductions of ambient temperature (Ta) to 15 degrees C by monitoring rate of heat production, rectal temperature, and skin temperature on the back, ear, and tail. These measurements were made in four rats while they were intact and during the 2 wk after cutaneous denervation. Rats were found to regulate body temperature well even after the cutaneous nerves of the trunk and face were sectioned. In eight rats the metabolic curve was determined before and 7-10 days after cutaneous denervation. Although the minimal resting metabolic rates did not differ in the two conditions, the lower critical temperature was significantly elevated from 26.8 to 28.9 degrees C and the rate of rise in metabolic rate per degrees celsius decrease in Ta was also significantly higher after cutaneous denervation. It appears that the higher rate of heat production is in compensation for an increase in the rate of heat loss in denervated rats.

Animals↗

Regulation of body temperature and energy requirements of hibernating alpine marmots (Marmota marmota).

Body temperature and metabolic rate were recorded continuously in two groups of marmots either exposed to seasonally decreasing ambient temperature (15 to 0 degrees C) over the entire hibernation season or to short-duration temperature changes during midwinter. Hibernation bouts were characterized by an initial 95% reduction of metabolic rate facilitating the drop in body temperature and by rhythmic fluctuations during continued hibernation. During midwinter, we observed a constant minimal metabolic rate of 13.6 ml O(2) x kg(-1) x h(-1) between 5 and 15 degrees C ambient temperature, although body temperature increased from 7.8 to 17.6 degrees C, and a proportional increase of metabolic rate below 5 degrees C ambient temperature. This apparent lack of a Q(10) effect shows that energy expenditure is actively downregulated and controlled at a minimum level despite changes in body temperature. However, thermal conductance stayed minimal (7.65 +/- 1.95 ml O(2) x kg(-1) x h(-1) x degrees C(-1)) at all temperatures, thus slowing down cooling velocity when entering hibernation. Basal metabolic rate of summer-active marmots was double that of winter-fasting marmots (370 vs. 190 ml O(2) x kg(-1) x h(-1)). In summary, we provide strong evidence that hibernation is not only a voluntary but a well-regulated strategy to counter food shortage and increased energy demands during winter.

Animals↗

CNS regulation of body temperature in euthermic and hibernating marmots (Marmota flaviventris).

Hypothalamic thermosensitivity of marmots was characterized during euthermia and hibernation. Hypothalamic temperature (Thy) was manipulated with chronically implanted, water-perfused thermodes while the animal's rate of oxygen consumption was continuously measured. The threshold Thy for eliciting an increase in metabolic heat production (MHP) and the proportionality constant (alphaMHP) relating rate of MHP to Thy were determined. In four euthermic marmots alphaMHP averaged -1.1 W-kg-1-degrees C-1. During the entrance into hibernation, as body temperature (Tb) declined from 36 to 8 degrees C, the threshold Thy for the MHP response progressively declined and was demonstrable at all times. The Thy of marmots in deep hibernation at an ambient temperature (Ta) of 5 degrees C plateaued near 7.5 degrees C, but threshold Thy for MHP showed a continuous slow decline of 0.2-0.4 degrees C a day, until one day prior to arousal. Proportional regulation of Tb was demonstrable at all times during deep hibernation. The average proportionality constant for the MHP response to hypothalamic cooling during deep hibernation in three marmots was -0.08 W-kg-1-degrees C-1. These results demonstrate that the hypothalamic regulator of Tb is active throughout hibernation and that there are progressive changes in its thermosensitivity.

Animals↗

Respiratory cooling and thermoregulatory coupling in reptiles.

Comparative physiological research on reptiles has focused primarily on the understanding of mechanisms of the control of breathing as they relate to respiratory gases or temperature itself. Comparatively less research has been done on the possible link between breathing and thermoregulation. Reptiles possess remarkable thermoregulatory capabilities, making use of behavioural and physiological mechanisms to regulate body temperature. The presence of thermal panting and gaping in numerous reptiles, coupled with the existence of head-body temperature differences, suggests that head temperature may be the primary regulated variable rather than body temperature. This review examines the preponderance of head and body temperature differences in reptiles, the occurrence of breathing patterns that possess putative thermoregulatory roles, and the propensity for head and brain temperature to be controlled by reptiles, particularly at higher temperatures. The available evidence suggests that these thermoregulatory breathing patterns are indeed present, though primarily in arid-dwelling reptiles. More importantly, however, it appears that the respiratory mechanisms that have the capacity to cool evolved initially in reptiles, perhaps as regulatory mechanisms for preventing overheating of the brain. Examining the control of these breathing patterns and their efficacy at regulating head or brain temperature may shed light on the evolution of thermoregulatory mechanisms in other vertebrates, namely the endothermic mammals and birds.

Adaptation, Physiological↗