Decline In Core Body Temperature Research Articles

Brown Adipose Tissue-Derived GDF15 Mediates Energy Homeostasis in a Sex-Dependent Manner

Growth differentiation factor 15 (GDF15) is a distant member of the transforming growth factor-β (TGFβ) superfamily that can be expressed in several tissues. Studies have shown that in response to prolonged high-fat feeding and cold stress GDF15 can be induced in brown adipocytes. Importantly, administration of recombinant GDF15 in rodents and non-human primates (Xiong, Y. et al. Long-acting MIC-1/GDF15 molecules to treat obesity: Evidence from mice to monkeys. Sci. Transl. Med. 9, eaan8732 (2017) reduces food intake and body mass. Indeed, we have recently shown that in a model of mitochondrial stress, brown adipose tissue (BAT)-derived GDF15 is required to maintain energy homeostasis and cold-induced thermogenesis in mice. Nonetheless, the role of BAT-derived GDF15 during physiological stress is not known. In the present study, we tested the hypothesis that BAT-derived GDF15 is required to regulate cold-induced thermogenesis and energy homeostasis in high-fat fed mice. To test this hypothesis, we generated mice selectively lacking GDF15 in thermogenic adipocytes (brown and beige) (GDF15 BKO). GDF15 BKO male and female mice had normal body weight, body composition and glucose homeostasis under baseline conditions. In response to 4 hours of cold exposure following fasting, the decline in core body temperature in GDF15 BKO female mice was similar to that observed in their wild type (WT) counterparts. Conversely, GDF15 BKO male mice became hypothermic. Surprisingly, after 12 weeks on a high-fat diet (HFD), GDF15 BKO female mice weighed significantly less and had reduced fat mass relative to their WT controls, while male mice had increased body weight and fat accumulation. Furthermore, resistance to DIO in female mice was associated with increased energy expenditure, while food intake and locomotor activity were unchanged. When ovariectomized, GDF15 BKO females experienced similar weight gain and fat accumulation as WT mice and no longer had increased energy expenditure. Of note, estrogen receptor alpha ( Esr1) expression in BAT was significantly repressed in GDF15 BKO male mice fed high-fat diet but was maintained in female mice relative to their respective WT controls. Taken together, our data suggest that GDF15 expression in BAT is dispensable for thermoregulation in female mice but is required to regulate core body temperature in males. Furthermore, while GDF15 BKO male mice are susceptible, female mice are resistant to DIO via mechanisms likely involving sex hormones and increased resting metabolic rates. NIH DK125405 to R.O.P.; Diabetes Research Training Program funded by the NIH (T32 DK112751) to JJ and by the NIH 1R25GM116686 to L.M.G.P. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

0095 Magnitude of Temperature Drop Prior to Sleep Onset May Predict Increase in Slow Wave Sleep

Abstract Introduction Neural circuitry implicated in thermoregulation is known to be interdependent with that implicated in regulation of sleep-wake state. In addition, previous studies in both rodent and human have shown that the sleep-associated decline in core body temperature (CBT) is associated with subsequent slow wave sleep. We sought to replicate this association in cognitively normal older adults, and extend upon previous studies by using automated telemetric methods to measure CBT. Methods Thirty-one cognitively normal and mildly cognitively impaired (MCI) older adults (age 68 ± 6 years, 18 female, 3 MCI) underwent measurement of CBT for two consecutive nights with a telemetric sensor, during which lab nocturnal polysomnography was simultaneously performed. Data from the second night were used. A validated algorithm was used to preprocess CBT to exclude and fill artifactual data outliers and small gaps, respectively. The sleep-associated CBT was calculated with an automated procedure by identifying the CBT decrease between the first peak in CBT identified prior to ‘Lights Out’ and the lowest value following Lights Out. Slow wave activity (SWA) increase was calculated as increase relative to baseline in the relative spectral power (0.5-4.0 Hz, F3-M2) in the first 5 second epoch following lights out. Results Of the 31 participants, 21 had both good quality EEG and CBT data, with an average total sleep time of 7.5 ± 1.5 hours, and an average duration 46.6 ± 18.5 hours of CBT data collected. There was a strong positive correlation between the magnitude of CBT decline and subsequent SWA (rho = 0.70, p < 0.001 Spearman’s Rank correlation), supporting previous results. Conclusion This is one of the first studies to obtain simultaneous CBT and NPSG data in older adults using an ingestible telemetric sensor. Our results support the previous research that there is a significant relationship between sleep-associated body cooling prior to sleep onset and increase in SWA. This highlights the potential for future therapeutic thermal intervention in older adults to improve sleep and sleep mediated health conditions. Further research with a bigger sample size will be necessary to control for variables such as obstructive sleep apnea and cognition status. Support (if any) NIH R01AG070866, R21AG055002, K25HL151912,

Novel temperature-controlled sleep system to improve sleep: aproof-of-concept study.

The sleep-wake cycle is regulated by circadian Process C and homeostatic Process S. Selective thermal stimulation (STS) of the cervical spine region enhances glabrous skin blood flow (GSBF) and augments body heat dissipation to increase distal-to-proximal skin gradient (DPG) causing decrease of core body temperature (CBT), which can shorten sleep onset latency (SOL) and improve sleep quality. A total of 11 young healthy/normal sleeper males challenged to go to bed (lights-off) 2 h earlier than usual were subjected in a randomised order to non-consecutive treatment and control night-time sleep sessions. The treatment night entailed activation of a dual-temperature zone mattress with a cooler centre and warmer periphery plus STS pillow that applied mild heating to the cervical spinal skin for 30 min after lights-off for sleep. During the first 30 min after lights-off, GSBF (mean [standard error (SE)] Δ=49.77[19.13]perfusion units, p=0.013) and DPG (mean [SE] Δ=2.05[0.62]°C, p= 0.005) were significantly higher and CBT (mean [SE] Δ=-0.15[0.07]°C, p=0.029) was significantly lower in the treatment than control night, while there was no significant difference in these variables during the 45 min prior to lights-off (baseline). Moreover, SOL was significantly reduced (mean [SE] Δ=-48.6[23.4]min, p=0.032) and subjective sleep quality significantly better (p < 0.001) in the treatment than control night. In conclusion, the novel sleep facilitating system comprised of the STS pillow plus dual-temperature zone mattress induced earlier increase in GSBF and DPG and earlier decline in CBT. This resulted in statistically significant shortened SOL and improved overall sleep quality, thereby reducing sleep pressure of Process S, even under the challenging investigative protocol requiring participants to go to sleep 2 h earlier than customary.

Sleep and Body Temperature

Mammals and birds seek a warm environment prior to sleep, which triggers vasodilatation and body cooling. Ambient temperatures outside the thermoneutral zone suppress sleep, particularly rapid eye movement (REM) sleep. We discuss the neurocircuit interactions associated with thermal and sleep regulation that occur primarily in the hypothalamic areas. An increase in ambient temperature stimulates the median preoptic/medial preoptic area of the hypothalamus, decreases body temperature, and increases non-REM sleep. Similarly, optical stimulation of the ventrolateral preoptic nucleus, which contains galanin (VLPOGAL), results in body cooling and non-REM sleep. A decrease in VLPOGAL disrupts sleep in elderly individuals and may also be associated with reduced decline in core body temperature during sleep. However, stimulation of neurons that synthesize melanin-concentrating hormone in the lateral hypothalamus decreases body temperature and induces REM sleep. We also discussed the acute effect of light on sleep induction and decreased body temperature, implicated with gamma-aminobutyric acid-ergic neurons in the preoptic area. Further investigation is needed to determine the mechanisms that induce physiological responses in diurnal and nocturnal species. These studies will contribute to a better understanding of the association between sleep and thermoregulation.

Evaluations of effects of sleep surfaces on athletic performance in youth

We recently demonstrated that sleeping on high rebound [HR] mattress toppers induced a continuous and more rapid decline in core body temperature compared to low rebound [LR] mattress toppers during the initial phase of nocturnal sleep in young healthy volunteers. HR toppers are characterized by their supportive feel and high breathability whereas LR toppers are pressure-absorbing. In the current study, we evaluated effects of HR mattress toppers on objectively-(actigraphy) and subjectively-(questionnaires) evaluated sleep, vigilance (psychomotor vigilance test), and athletic performance (40-m sprint time, long jump distance, and star drill time) in youth male athletes age 10–19, in two sessions: fifty-one subjects in 2013 (study I) and 23 subjects in 2014 (study II). Sleeping on HR mattress toppers for four to six weeks improved some athletic performance measures compared to sleeping on LR or sleeping directly on spring mattresses without a topper. Statistically significant improvements in 40-m sprint time in study I (compared to LR) and in star drill time in study II (no topper) were observed. No changes in sleep and psychomotor vigilance were observed. These results suggest selecting optimal sleep surfaces may contribute to the maximization of athletic performances, and further studies are warranted.

Ambulatory Estimation of Circadian Rhythms Shows Core Body Temperature Phase Precedes Slow Wave Sleep Phase in the Normal Elderly

Evidence suggests that age-related reductions in slow wave sleep (SWS) are associated with increased risk for Alzheimer’s disease (AD), making it important to understand how SWS is regulated. Evidence also indicates a strong interdependence between SWS onset and a decline in core body temperature (CBT), but causal mechanisms are not understood. We aimed to determine the temporal relationship between CBT and slow-wave activity (SWA) in the normal elderly.

HuR expression in adipose tissue mediates energy expenditure and acute thermogenesis independent of UCP1 expression

ABSTRACT The goal of this study was to define the functional role of adipocyte-specific expression of the RNA binding protein Human antigen R (HuR). Mice with an adipocyte-specific deletion of HuR (Adipo-HuR−/- ) were generated by crossing HuR floxed (HuRfl/fl ) mice with mice expressing adiponectin-driven cre-recombinase (Adipoq-cre). Our results show that Adipo-HuR−/- mice display a lean phenotype compared to wild-type littermate controls. HuR deletion results in a diet-independent reduction in percent body fat composition along with an increase in energy expenditure. Functionally, Adipo-HuR−/- mice show a significant impairment in acute adaptive thermogenesis (six hours at 4°C), but uncoupling protein 1 (UCP1) protein expression in brown adipose tissue (BAT) is unchanged compared to control. Pharmacological inhibition of HuR also results in a marked decline in core body temperature following acute cold challenge independent of UCP1 protein expression. Among the 588 HuR-dependent genes in BAT identified by RNA-seq analysis, gene ontology analysis shows a significant enrichment in mediators of calcium transport and signalling, almost all of which are decreased in Adipo-HuR−/- mice compared to control. In conclusion, adipocyte expression of HuR plays a central role in metabolic homoeostasis and mediates UCP1-independent thermogenesis in BAT, potentially through post-transcriptional control of intracellular calcium transport.Abbreviations: Adipo-HuR−/-: Adipocyte-specific HuR deletion mice; BAT: Brown adipose tissue; HuR: Human antigen R; UCP1: Uncoupling protein 1

Effects of sleep on a high-heat capacity mattress on sleep stages, EEG power spectra, cardiac interbeat intervals and body temperatures in healthy middle-aged men‡.

This study deals with the question whether a slow (non-disturbing) reduction of core body temperature (CBT) during sleep increases sleep stage N3 and EEG slow wave energy (SWE) and leads to a slowing of heart rate in humans. Thirty-two healthy male subjects with a mean ± SD age 46 ± 4 years and body mass index 25.2 ± 1.8 kg/m2. A high-heat capacity mattress (HM) was used to lower body temperatures in sleep and was compared to a conventional low-heat capacity mattress (LM) in a double-blinded fashion. Polysomnography was performed accompanied by measurements of skin-, core body- and mattress surface-temperatures, and heart rate. EEG power spectral analyses were carried out using Fast Fourier Transform. Interbeat intervals were derived from the electrocardiogram. The HM led to a larger decline in CBT, mediated through higher heat conduction from the core via the proximal back skin onto the mattress together with reduced heart rate. These effects occurred together with a significant increase in sleep stage N3 and standardized slow wave energy (sSWE, 0.791-4.297 Hz) accumulated in NREM sleep. In the 2nd half of the night sSWE increase was significantly correlated with body temperature changes, for example with CBT decline in the same phase. A HM subtly decreases CBT, leading to an increased amount of sleep stage N3 and of sSWE, as well as a slowing of heart rate.

High rebound mattress toppers facilitate core body temperature drop and enhance deep sleep in the initial phase of nocturnal sleep.

Recently, several new materials for mattresses have been introduced. Although some of these, such as low rebound (pressure-absorbing/memory foam) and high rebound mattresses have fairly different characteristics, effects of these mattresses on sleep have never been scientifically evaluated. In the current study, we have evaluated effects of a high rebound mattress topper [HR] on sleep and its associated physiology, and the effects were compared to those of a low rebound mattress toppers (LR) in healthy young (n = 10) and old (n = 20) adult males with a randomized, single-blind, cross over design. We found that sleeping with HR compared to LR induced a larger decline in core body temperature (CBT) in the initial phase of nocturnal sleep both in young (minimum CBT: 36.05 vs 36.35°C) and old (minimum CBT: 36.47 vs. 36.55°C) subjects, and declines in the CBT were associated with increases in deep sleep/delta power (+27.8% in young and +24.7% in old subjects between 11:00–01:00). We also found significantly smaller muscle activities during roll over motions with HR (-53.0 to -66.1%, depending on the muscle) during a separate daytime testing. These results suggest that sleeping with HR in comparison to with LR, may facilitate restorative sleep at the initial phase of sleep.

Sleep on a high heat capacity mattress increases conductive body heat loss and slow wave sleep

Environmental temperature can strongly affect sleep. The habitual sleep phase is usually located between evening decline and morning rise of the circadian rhythm of core body temperature (CBT). However, the thermophysiological mechanisms promoting or disturbing sleep are not yet fully understood. The purpose of this study was to examine the effects of a high heat capacity mattress (HHCM) on CBT, skin temperatures and sleep in comparison to a conventional low heat capacity mattress (LHCM). Based on the higher heat capacity of HHCM an increase in conductive body heat loss enhances the nocturnal decline in CBT can be expected. Based on previous findings this may then be accompanied by an increase in slow wave sleep (SWS).The mattresses were studied in a randomized single-blind crossover design in fifteen healthy young men (Age: 26.9±2.1yr, BMI: 22.2±0.4kg/m2) by overnight in laboratory standard video-polysomnography in a temperature stabilized setting. CBT, room temperature, and skin and mattress surface temperatures were continuously recorded in order to get information about inner and outer body heat flow. Additionally, subjective sleep quality was estimated by visual analogue scale.In comparison to LHCM sleep on HHCM exhibited a selective increase in SWS (16%, p<0.05), increased subjective sleep quality and sleep stability [reduced cyclic alternating pattern (CAP) rate; 5.3%, p<0.01]. Additionally, analyses of the sleep stages showed in the second part of the night a significant increase in SWS and a decrease in REMS. In addition, HHCM induced a greater reduction in CBT (maximally by −0.28°C), reduced the increase in proximal skin temperatures on the back (PROBA; maximally by −0.98°C), and delayed the increase in mattress surface temperature (maximal difference LHCM-HHCM: 6.12°C). Thus, the CBT reduction can be explained by an increase in conductive heat loss to the mattress via proximal back skin regions. Regression analysis identified PROBA as the critical variable to predict inner conductive heat transfer from core to shell and SWS.In conclusion, the study expands the previous findings that a steeper nocturnal decline in CBT increases SWS and subjective sleep quality, whereas inner conductive heat transfer could be identified as the crucial thermophysiological variable, and not CBT.

The influence of light on thermal responses.

Light is essential for vision and plays an important role in non-visual responses, thus affecting alertness, mood and circadian rhythms. Furthermore, light influences physiological processes, such as thermoregulation, and therefore may be expected to play a role in thermal comfort (TC) as well. A systematic literature search was performed for human studies exploring the relation between ocular light exposure, thermophysiology and TC. Experimental results show that light in the evening can reduce melatonin secretion, delay the natural decline in core body temperature (CBT) and slow down the increase in distal skin temperature. In the morning though, bright light can result in a faster decline in melatonin levels, thus enabling a faster increase in CBT. Moreover, the colour of light can affect temperature perception of the environment. Light with colour tones towards the red end of the visual spectrum leads to a warmer perception compared to more bluish light tones. It should be noted, however, that many results of light on thermal responses are inconclusive, and a theoretical framework is largely lacking. In conclusion, light is capable of evoking thermophysiological responses and visual input can alter perception of the thermal environment. Therefore, lighting conditions should be taken into consideration during thermophysiological research and in the design of indoor climates.

Altered Responses to Cold Environment in Urocortin 1 and Corticotropin-Releasing Factor Deficient Mice

We examined core body temperature (CBT) of urocortin 1 (UCN1) and corticotropin releasing factor (CRF) knockout (KO) mice exposed to 4°C for 2 h. UCN1KO mice showed higher average CBT during cold exposure as compared to WT. The CBT of male and female WT mice dropped significantly to34.1 ± 2.4and34.9 ± 3.1 C at 4°C, respectively. In contrast, the CBT of male and female UCN1KO mice dropped only slightly after 2 h at 4°C to36.8 ± 0.7and38.1 ± 0.5 C, respectively. WT female and male UCN1KO mice showed significant acclimatization to cold; however, female UCN1KO mice did not show such a significant acclimatization. CRFKO mice showed a dramatic decline in CBT from38.2 ± 0.4at 22°C to26.1 ± 9.8at 4°C for 2 h. The CRF/UCN1 double KO (dKO) mice dropped their CBT to32.5 ± 4.0after 2 h exposure to 4°C. Dexamethasone treatment prevented the decline in CBT of the CRFKO and the dKO mice. Taken together, the data suggest a novel role for UCN1 in thermoregulation. The role of CRF is likely secondary to adrenal glucocorticoids, which have an important regulatory role on carbohydrate, fat, and protein metabolism.

Circadian Body Temperature Variability is an Indicator of Poor Prognosis in Cardiomyopathic Hamsters

BackgroundLow body temperature is an independent predictor of poor prognosis in patients with congestive heart failure. The cardiomyopathic hamster develops progressive biventricular dysfunction, resulting in heart failure death at 9 months to 1 year of life. Our goal was to use cardiomyopathic hamsters to examine the relationship between body temperature and heart failure decompensation and death. Methods and ResultsTo this end, we implanted temperature and activity transducers with telemetry into the peritoneal space of 46 male Bio-TO-2 Syrian cardiomyopathic hamsters. Multiple techniques, including computing mean temperature, frequency domain analysis, and nonlinear analysis, were used to determine the most useful method for predicting poor prognosis. Data from 44 hamsters were included in our final analysis. We detected a decline in core body temperature in 98% of the hamsters 8±4 days before death (P < .001). We examined the dominant frequency of temperature variation (ie, the circadian rhythm) by using cosinor analysis, which revealed a significant decrease in the amplitude of the body temperature circadian rhythm 8 weeks before death (0.28°C; 95% CI, 0.26-0.31) compared to baseline (0.36°C; 95% CI, 0.34-0.39; P=.005). The decline in the circadian temperature variation preceded all other evidence of decompensation. ConclusionsWe conclude that a decrease in the amplitude of the body temperature circadian rhythm precedes fatal decompensation in cardiomyopathic hamsters. Continuous temperature monitoring may be useful in predicting preclinical decompensation in patients with heart failure and in identifying opportunities for therapeutic intervention.

Liver Genomic Responses to Ciguatoxin: Evidence for Activation of Phase I and Phase II Detoxification Pathways following an Acute Hypothermic Response in Mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p < or = 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (/fold change/ > or = 1.5 and p < or = 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4 degrees C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice.

Melatonin: Characteristics, Concerns, and Prospects

Melatonin is of great importance to the investigation of human biological rhythms. Its rhythm in plasma or saliva provides the best available measure of the timing of the internal circadian clock. Its major metabolite 6-sulphatoxymelatonin is robust and easily measured in urine. It thus enables long-term monitoring of human rhythms in real-life situations where rhythms may be disturbed, and in clinical situations where invasive procedures are difficult. Melatonin is not only a "hand of the clock"; endogenous melatonin acts to reinforce the functioning of the human circadian system, probably in many ways. Most is known about its relationship to sleep and the decline in core body temperature and alertness at night. Current perspectives also include a possible influence on major disease risk, arising from circadian rhythm disruption. Melatonin clearly has the ability to induce sleepiness and lower core body temperature during "biological day" and to change the timing of human rhythms when treatment is appropriately timed. It can entrain free-running rhythms and maintain entrainment in most blind and some sighted people. Used therapeutically it has proved a successful treatment for circadian rhythm disorder, particularly the non-24-h sleep wake disorder of the blind. Numerous other clinical applications are under investigation. There are, however, areas of controversy, large gaps in knowledge, and insufficient standardization of experimental conditions and analysis for general conclusions to be drawn with regard to most situations. The future holds much promise for melatonin as a therapeutic treatment. Most interesting, however, will be the dissection of its effects on human genes.

Prolonged Mild Hypoxia Modifies Human Circadian Core Body Temperature and may be Associated with Sleep Disturbances

Fatigue is often reported after long-haul airplane flights. Hypobaric hypoxia, observed in pressurized cabins, may play a role in this phenomenon by altering circadian rhythms. In a controlled cross-over study, we assessed the effects of two levels of hypoxia, corresponding to cabin altitudes of 8000 and 12,000 ft, on the rhythm of core body temperature (CBT), a marker of circadian rhythmicity, and on subjective sleep. Twenty healthy young male volunteers were exposed for 8 h (08:00–16:00 h) in a hypobaric chamber to a cabin altitude of 8000 ft and, 4 weeks later, 12,000 ft. Each subject served as his own control. For each exposure, CBT was recorded by telemetry for two 24 h cycles (control and hypoxic exposure). After filtering out nonphysiological values, the individual CBT data were fitted with a five-order moving average before statistical group analysis. Sleep latency, sleep time, and sleep efficiency were studied by sleep logs completed every day in the morning. Our results show that the CBT rhythm expression was altered, mainly at 12,000 ft, with a significant increase of amplitude and a delay in the evening decline in CBT, associated with alterations of sleep latency. Mild hypoxia may therefore alter circadian structure and result in sleep disturbances. These results may explain in part the frequent complaints of prolonged post-flight fatigue after long flights, even when no time zones are crossed.

Sympathetic activation by fenfluramine depletes brown adipose tissue norepinephrine content in rats

The antiobesity agent fenfluramine (FEN) has been reported to produce an activation of sympathetic neurons to brown adipose tissue (BAT) resulting in thermogenesis. The present study was conducted to determine if FEN-induced activation of BAT is affected by the ambient temperature at which animals are maintained. Body temperature was determined in conscious male Sprague–Dawley rats using implanted temperature transmitters, and sympathetic activation of BAT was determined by measuring norepinephrine (NE) content. Animals maintained at 22 and 4 °C incurred a significant decline in core body temperature following FEN administration. FEN produced a significant depletion of BAT NE content, and the magnitude of BAT NE depletion was related to the dose of FEN (−57.4% at 3 mg/kg dose and −75.9% at 10 mg/kg dose). However, the extent of BAT NE depletion was equal at 22 and 4 °C. BAT NE depletion by FEN appears to depend on activation of sympathetic neurons because it was prevented by pretreatment with the ganglionic blocker pentolinium (10 mg/kg ip). Furthermore, NE depletion by FEN could be blocked with fluoxetine (10 mg/kg ip) pretreatment, indicating that the action of FEN is mediated through the release of serotonin.

Mental and Cognitive Performance in the Cold

ABSTRACTVigilance, attention, memory, and motivation are essential to adapting to the physiological changes that occur with prolonged exposure to the cold and to avoiding both the environmental hazards associated with cold and the health-related consequences of these hazards, This paper summarizes the effects of cold temperatures on cognitive performance and mood. Although the effects of hypothermic-induced cold temperatures on cognitive performance and mood have been well documented, evidence of nonhypothermic effects has been inconsistent. There is evidence of a dose-response relation involving decrements in cognitive performance with respect to decline in core body temperature and complexity of tasks performed. However, it is unclear whether these effects are due to distraction or increased arousal. Likewise, further research is required to test the efficacy of existing and proposed pharmacologic and nutritional countermeasures. (Int J Circumpolar Health 2001; 60: 430-439)

The hypothermic effect of late evening melatonin does not block the phase delay induced by concurrent bright light in human subjects

This constant routine study ( n=9 men) compared the phase delay of the circadian system induced by a single pulse of evening light (5000 lx at 2100–2400 h) in the presence or absence of exogenous melatonin (5 mg p.o. at 2040 h). On the treatment day, light and melatonin protracted and accelerated, respectively, the evening decline in core body temperature (CBT). Subjective sleepiness ratings showed parallel shifts, the earlier the decline in CBT, the sleepier. On the post-treatment day, light induced a phase delay in the mid-range crossing time of CBT decline independent of whether melatonin was co-administered or not. Subjective sleepiness was delayed in parallel. The phase delay of the circadian system by evening light appears to be independent of an immediate hyperthermic effect and is not mediated by melatonin.

Early evening melatonin and S-20098 advance circadian phase and nocturnal regulation of core body temperature

The phase-shifting capacity and thermoregulatory effects of a single oral administration at 18 h of melatonin (5 mg) or S-20098, a melatonin agonist (5 or 100 mg), was investigated in eight healthy young men in a double-blind placebo crossover design. The unmasking conditions of a shortened constant-routine protocol (mini-CR) were used to collect evening phase markers of physiological parameters. In comparison to placebo, all three drug administrations induced an earlier dim-light melatonin onset (DLMO), an earlier increase in distal skin temperature, and an earlier decrease in core body temperature (CBT), heart rate, and proximal skin temperature. This indicates that administration at 18 h of both melatonin and S-20098 (more pronounced with 100 than 5 mg) induced an earlier regulation of the endogenous circadian nocturnal decline in CBT. On the posttreatment day a second mini-CR revealed persistent significantly phase-advanced circadian rhythms as estimated by DLMO, as well as by the midrange crossing time of CBT and heart rate decline. There were no significant differences between the two doses of S-20098. The data suggest that, in addition to immediate thermoregulatory changes, a phase advance of the circadian system had occurred and that the phase advance could still be measured on the posttreatment day.