Effects Of Elevated Body Temperature Research Articles

Deletion of UCP1 in Tg2576 Mice Increases Body Temperature and Exacerbates Alzheimer's Disease-Related Pathologies.

We previously demonstrated that the Alzheimer's disease (AD)-like model mice, Tg2576, housed at a high ambient temperature of 30 °C for 13 months, exhibited increased body temperature, which increased amyloid-β (Aβ) levels and tau stability, leading to tau phosphorylation and ultimately inducing memory impairment. Here, we aimed to exclude the possible effect of environmental factors associated with the difference in ambient temperature (23 °C vs. 30 °C) and to further clarify the effects of elevated body temperature on AD-like pathologies. We generated uncoupling protein 1 (UCP1) deletion in Tg2576 mice, Tg2576/UCP1-/-, because UCP1 deletion mice show a sustained rise in body temperature at normal room temperature. As expected, the body temperature in Tg2576/UCP1-/- mice was higher than that in Tg2576/ UCP1+/+ mice at 23 °C, which was accompanied by upregulated Aβ levels due to increased β-secretase (BACE1) and decreased neprilysin (NEP) protein levels in the brains of Tg2576/UCP1-/- mice compared with those in the Tg2576/ UCP1+/+ mice. Elevated body temperature also increased total tau levels, leading to enhanced phosphorylation, heat shock protein induction, and activated tau kinases. Furthermore, elevated body temperature enhanced glial activation and decreased synaptic protein levels in the brain. Taken together, these findings demonstrate that elevated body temperatures exacerbate AD-like pathologies.

Effects of Elevated Body Temperature on Selected Physiological Indices and Thermal Stress in Athletes and Non-Athletes.

The purpose of this study was to determine the effects of active and passive overheating. A group of athletes (A) and non-athletic men (N) underwent an exercise stress test at elevated ambient temperature and sauna bathing until an increase in rectal temperature of 1.2°C was observed. It was shown that group A performed physical exercise for a longer period of time, which elicited significantly higher amounts of work performed in the stress test. Both forms of overheating caused a significant decrease in BM and a significant change in plasma volume, while greater dehydration was observed after active overheating. Changes observed in group A were higher than in group N. MCV levels were initially higher in group A. The levels in both groups decreased after sauna bathing, although in non-athletes the decrease was greater. Both forms of overheating increased Hb, HCT, and SBP, while only the non-athletic group showed a decrease in DBP after the exercise stress test. However, a decrease in DBP was observed in both groups after sauna bathing. The PSI increased after both tests, yet to a higher extent after the stress test than after sauna bathing. The PSI was negatively correlated with VO2max in both groups. The increase in cortisol concentration was higher after sauna bathing. There was a correlation between cortisol levels and the work performed during the stress test in group A. Endurance training resulted in more efficient thermoregulatory mechanisms in athletes.

Reproductive physiology of the heat-stressed dairy cow: implications for fertility and assisted reproduction.

Heat stress causes a large decline in pregnancy success per insemination during warm times of the year. Improvements in fertility are possible by exploiting knowledge about how heat stress affects the reproductive process. The oocyte can be damaged by heat stress at the earliest stages of folliculogenesis and remains sensitive to heat stress in the peri-ovulatory period. Changes in oocyte quality due to heat stress are the result of altered patterns of folliculogenesis and, possibly, direct effects of elevated body temperature on the oocyte. While adverse effects of elevated temperature on the oocyte have been observed in vitro, local cooling of the ovary and protective effects of follicular fluid may limit these actions in vivo. Heat stress can also compromise fertilization rate. The first seven days of embryonic development are very susceptible to disruption by heat stress. During these seven days, the embryo undergoes a rapid change in sensitivity to heat stress from being very sensitive (2- to 4-cell stage) to largely resistant (by the morulae stage). Direct actions of elevated temperature on the embryo are likely to be an important mechanism for reduction in embryonic survival caused by heat stress. An effective way to avoid effects of heat stress on the oocyte, fertilization, and early embryo is to bypass the effects through embryo transfer because embryos are typically transferred into females after acquisition of thermal resistance. There may be some opportunity to mitigate effects of heat stress by feeding antioxidants or regulating the endocrine environment of the cow but neither approach has been reduced to practice. The best long-term solution to the problem of heat stress may be to increase genetic resistance of cows to heat stress. Thermotolerance genes exist within dairy breeds and additional genes can be introgressed from other breeds by traditional means or gene editing.

Abstract 790: Are laboratory mice too cold to mount effective anti-tumor immune responses

Abstract During the course of experiments to determine the effects of elevated body temperature on anti-tumor immune responses, we unexpectedly observed that in control animals bearing tumors and maintained under standard room temperatures (IACUC-compliant, 21-23°C), the core temperature actually began to fall significantly as the tumors grew larger. Moreover, using thermal preference analyses, we found that animals bearing tumors exhibit considerable heat-seeking behavior. In an attempt to keep body temperature within the normal range (∼37°C), we began to house tumor bearing mice in a warmer environment (i.e., 28-30°C) considered to be the thermoneutral temperature for mice, as apposed to IACUC compliant temperatures which are considered mildly hypothermic for mice. Decisions that have resulted in the mildly cooler environmental temperature required in animal colonies have been generally based upon optimizing air-handling capacity of fumes and the thermal comfort of personnel rather than the optimal thermal comfort of animals (hence the requirements for multiple mice per cage to allow for huddling). When we analyzed tumor growth under thermoneutral conditions, syngeneic tumor growth was significantly delayed in animals maintained at 28-30°C compared to tumor growth in animals maintained at 21-23 oC. If the same comparison is made using SCID mice, no difference in tumor growth rate is observed. More specifically, BALB/c, C57BL/6 and SCID mice were housed in either standard room temperature (RT = 21-23°C) or in a warmer ambient temperature (WR = 28-30°C). Mice were then implanted with a syngeneic tumor (CT26 for BALB/c and SCID; B16.F10 for C57BL/6) subcutaneously and tumor growth was monitored. Tumor growth in C57BL/6 and BALB/c mice was inhibited when mice were housed in the warmer ambient temperature compared to animals maintained in standard room temperature. There was no difference in CT26 tumor growth in SCID mice. This finding suggested that the T cell-dependent anti-tumor immune response may be at least partly responsible for enhanced tumor growth control under conditions of warmer ambient temperature. Results of depletion studies in C57BL/6 mice bearing B16.F10 tumors, showed that both CD4+ and CD8+ T cells were required for inhibition of tumor growth in the warmer ambient temperature. In BALB/c mice bearing CT26 tumors, only CD8+ T cells were required to inhibit tumor growth. These findings suggest that the natural anti-tumor immune response exhibited by mice housed in standard colony conditions is sub-optimal and can be improved simply by housing mice under thermoneutral conditions. T cell dependent anti-tumor immunity appears to be at least one immune mechanism which is improved when animals are not cold stressed. Supported by NIH R01 CA 135368. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 790. doi:10.1158/1538-7445.AM2011-790

Effects of Elevated Body Temperature on Control of Breathing

Effects of Elevated Body Temperature on Control of Breathing Changes in body temperature can be evoked mainly by alterations in the peripheral temperature, or modified by shifts in the central body temperature. Two conditions can lead to abnormal elevation of body temperature: hyperthermia or fever. As regards respiratory system, exposure to heat stress is accompanied by marked alterations in breathing, especially by an increase in ventilation. Ventilation rises due to an increase in central output from hypothalamus or brainstem, an increase in peripheral output via skin temperature receptors, an increase in central or/and peripheral chemoreceptor output or sensitivity and can be also mediated through changes in thermoregulatory mechanisms. This review summarizes results of previous studies as well as of experiments done in our laboratory in order to elucidate the mechanisms included in respiratory changes under heat stress.

Effect of hyperthermia and anoxia on glucocorticoid and mineralocorticoid receptor expression in neonatal rat hippocampus

Brief periods of neonatal asphyxia are frequently observed. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia. The hippocampus contains the highest concentration of both mineralocorticoid (MR) and glucocorticoid (GR) receptors and the balance between MR/GR activation influences cell birth and death. MR occupation appears to promote prosurvival actions, while GR overactivation favours neurodegeneration. It has been widely recognized that core body temperature is a critical determinant of the severity of hypoxic–ischemic brain injury; indeed, hyperthermia exacerbates the degree of damage. Therefore, the aim of the present investigation was to study the effect of elevated body temperature in newborn rats under control conditions or during neonatal exposure to a critical anoxia, on changes of MR and GR mRNA expression in the rat hippocampus. 2-day-old rats were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33°C (typical for the rat neonates), or elevated to a level typical for febrile (39°C) adults. Control rats were exposed to atmospheric air under the respective thermal conditions. The changes in MR and GR mRNA expression in hippocampus were examined 24h after exposure. Our data show that hyperthermia with or without added anoxia, causes induction of MR mRNA expression in neonatal rat hippocampus without any effect on GR mRNA expression. We suggest this elevation of MR plays an important role in modulating the survival of neurons in the injured hippocampus.

Thermal stress on intertidal limpets: long-term hindcasts and lethal limits

When coupled with long-term meteorological records, a heat-budget model for the limpet, Lottia gigantea, provides a wealth of information regarding environmental and topographic controls of body temperature in this ecologically important species. (1) The maximum body temperature predicted for any site (37.5 degrees C) is insufficient to kill all limpets, suggesting that acute thermal stress does not set an absolute upper limit to the elevation of L. gigantea on the shore. Therefore, the upper limit must be set by behavioral responses, sublethal effects or ecological interactions. (2) Temperatures sufficient to kill limpets are reached at only a small fraction of substratum orientations and elevations and on only three occasions in 5 years. These rare predicted lethal temperatures could easily be missed in field measurements, thereby influencing the interpretation of thermal stress. (3) Body temperature is typically higher than air temperature, but maximum air temperature can nonetheless be used as an accurate predictor of maximum body temperature. Warmer air temperatures in the future may thus cause increased mortality in this intertidal species. Interpretation of the ecological effects of elevated body temperature depends strongly on laboratory measurements of thermal stress, highlighting the need for additional research on the temporal and spatial variability of thermal limits and sublethal stress. The lengthy time series of body temperatures calculated from the heat-budget model provides insight into how these physiological measurements should be conducted.

Susceptibility of bovine germinal vesicle-stage oocytes from antral follicles to direct effects of heat stress in vitro.

Delineation of maternal versus direct effects of heat stress in reducing development at the germinal vesicle (GV) stage is challenging, because oocytes spontaneously resume meiosis after removal from antral follicles. The use of S-roscovitine (inhibitor of p34(cdc2)/cyclin B kinase) to hold bovine oocytes at the GV stage without compromising early embryo development was previously validated in our laboratory. The objective of the present study was to assess the direct effects of an elevated temperature commonly seen in heat-stressed dairy cows on cumulus-oocyte complexes (COCs) held at the GV stage using 50 microM S-roscovitine. During roscovitine culture, GV-stage COCs (antral follicle diameter, 3-8 mm) were cultured at 38.5 or 41 degrees C. Thereafter, oocytes were removed from roscovitine medium and allowed to undergo in vitro maturation, fertilization, and culture. Zona pellucida hardening (solubility to 0.5% pronase), nuclear stage (Hoechst 33342), cortical granule type (lens culinaris agglutinin-fluorescein isothiocyanate [FITC]), and early embryo development were evaluated. Culture of GV-stage COCs at 41 degrees C increased the proportion that had type III cortical granules and reduced the proportion that progressed to metaphase II after in vitro maturation. Effects of 41 degrees C on zona pellucida hardening, fertilization (penetration, sperm per oocyte, pronuclear formation, and monospermic and putative embryos), and cleavage of putative zygotes were not noted. However, culture of GV-stage COCs at 41 degrees C for 6 h decreased the proportion of 8- to 16-cell embryos, whereas 41 degrees C for 12 h reduced blastocyst development. In summary, antral follicle COCs are susceptible to direct effects of elevated body temperature, which may account in part for reduced fertility in heat-stressed cows.

Fever: a possible strategy for membrane homeostasis during infection.

Although there is a generally accepted belief that fever has survival value in infection, the molecular mechanism behind the beneficial effects of elevated body temperature during disease has not been established. A substantial body of experimental studies and theoretical grounds concerning the benefit of fever considers the incremental effect of elevated temperature on various metabolic processes, including the immune system, as well as the attenuation of the viability of some pathogenic microorganisms at febrile temperature [1, 2]. Also, the evidence that fever occurs across a broad spectrum of the zoological kingdom conveys the impression that fever must be a beneficial physiological response to infection that has persisted in evolution [3, 4]. Considering the accumulated evidence Kluger [4] has said, Fever evolved as an adaptive host-defense response. Nevertheless, debate about the biological value of fever continues. In this paper I put forward the hypothesis that besides the effect of temperature on various host-defense responses [5], fever also could be considered a homeostatic process in terms of maintenance of a constancy of cell membrane in the infected organism. Membrane condition is interpreted as a physical state of cell surface assigned to a functional interrelationship of two essential factors: (1) composition of the membrane's lipid components, and (2) actual temperature of the membrane. Specific physiological interplay of these two factors accounts for dynamic equilibrium of membrane with the environment and, in

Changes in semen quality in the stallion following experimental infection with equine arteritis virus

Two groups of eight stallions each, comprising separate experiments, were inoculated intranasally with equine arteritis virus (EAV) to investigate its effects on semen quality. Semen from each stallion was evaluated two to four times per week on the basis of semen volume, and on sperm concentration, motility and morphology. Significant decreases in motility, concentration and the percentage of normal spermatozoa were detected in the stallions in Experiment 2. A decrease in the percentage of normal spermatozoa was the only significant finding in the stallions in Experiment 1. The changes in semen quality observed in these stallions were considered to have resulted from the combined thermal effects of elevated body temperature and scrotal edema following infection with EAV and were not regarded as virus-specific in nature.

Body temperature modulates the effect of platelet-activating factor (PAF) on airways responsiveness in the rabbit

Platelet-activating factor (PAF) is a potent mediator known to cause bronchoconstriction and increase airways responsiveness. In vitro studies have shown that the effects of PAF on cell function can be very temperature-dependent. The aim of the current study was to investigate the effect of elevated body temperature on numbers of circulating cells and pulmonary function in anesthetized rabbits in response to PAF. PAF was given intravenously, at a dose of 1.2 micrograms/kg hour, whereas the control experiments were performed after the animals received a saline infusion. Alteration of airways function was assessed by measuring specific pulmonary conductance (SGL) and dose-response relationships to inhaled histamine, where airways responsiveness was expressed as the effective concentration causing 50% of maximal change in specific airways conductance (EC50SGL). The rabbits were studied at two body temperatures: a normal temperature (rectal temperature of 39.8 C), and a higher temperature (rectal temperature 41.2 degrees C). Changes in circulating inflammatory cells, plasma corticosterone concentrations and in hematocrit were also monitored, to examine some potential mechanisms which might explain why body temperature altered airways responsiveness. At the normal body temperature infusion of PAF caused a significant increase in airways responsiveness (p less than 0.025), while at the high body temperature, there was a significant decrease in responsiveness (p less than 0.025). However, at both body temperatures, a profound but similar thrombocytopenia and neutropenia was observed. While plasma corticosterone levels and hematocrit showed increases coincident with the infusion of PAF, this response was unchanged by altering body temperature. We conclude that increased body temperature reduces the effect of PAF on airways responsiveness apparently through a mechanism independent of PAF effects on hemoconcentration, plasma corticosterone or circulating inflammatory cells.

Effect of elevated body temperature on the pharmacokinetics of gentamicin in the dog.

Effect of elevated body temperature on the pharmacokinetics of gentamicin in the dog.

Effect of continuous and intermittent elevated temperatures on thein vitrogrowth ofBlastomyces dermatitidis

The growth characteristics of 9 isolates of Blastomyces dermatitidis were studied at temperatures ranging from 35° C. to 43° C. Generation time ranged from 9–12 hr. Minimum generation time and maximum total growth did not necessarily occur at the same temperature. Maximum total growth was obtained at 35° C. with 5 isolates and at 37° C. with 4 isolates. All of the isolates grew well at 39° C. and only 1 isolate failed to grow at 41° C. Eight of the 9 isolates grew at 42° C. and a minimal amount of growth was obtained with 1 isolate at 43° C. Isolates growing at 37° C. were subjected intermittently to elevated temperatures of 39° C. and 41° C. in order to determine the effect on growth rate and total growth. The results are discussed in relation to published observations on the inhibitory effect of elevated body temperature and experimental mycoses in animals.

Effect of Elevated Body Temperature on Plasma Vitamin A and Carotene.

In a study of 92 patients it was found that elevation of the body temperature to 105.5° or 106.0°F (rectal) by physically induced fever was followed by a depression of the plasma vitamin A and carotene. The extent of the depression was directly related to the duration of the fever. The course of the plasma vitamin A and carotene was almost identical irrespective of the chemo-therapeutic agents (bismuth subsalicylate in oil, mapharsen, sulfathiazole or the sodium salt of penicillin) given either before or during physically-induced fever of equal duration. It is, therefore, justifiable to conclude that elevation of the body temperature is the principal cause of the depression of plasma vitamin A and carotene. At the termination of fever, the plasma vitamin A was nearly at the lowest level. The restoration of the plasma vitamin A level usually occurred by the second day after treatment and took place spontaneously without any special medication or dietary measures. The plasma carotene level showed a pattern similar to that of the plasma vitamin A. The depression of the carotene was generally not as great and occurred more slowly. This behavior of the plasma vitamin A is, to the best of our knowledge, the first biochemical indicator shown to serve as a measurement of the intensity of the action of physically-induced fever on the human organism.