Yuki Uchida

Relative importance of different surface regions for thermal comfort in humans

In a previous study, we investigated the contribution of the surface of the face, chest, abdomen, and thigh to thermal comfort by applying local temperature stimulation during whole-body exposure to mild heat or cold. In hot conditions, humans prefer a cool face, and in cold they prefer a warm abdomen. In this study, we extended investigation of regional differences in thermal comfort to the neck, hand, soles, abdomen (Experiment 1), the upper and lower back, upper arm, and abdomen (Experiment 2). The methodology was similar to that used in the previous study. To compare the results of each experiment, we utilized the abdomen as the reference area in these experiments. Thermal comfort feelings were not particularly strong for the limbs and extremities, in spite of the fact that changes in skin temperature induced by local temperature stimulation of the limbs and extremities were always larger than changes that were induced in the more proximal body parts. For the trunk areas, a significant difference in thermal comfort was not observed among the abdomen, and upper and lower back. An exception involved local cooling during whole-body mild cold exposure, wherein the most dominant preference was for a warmer temperature of the abdomen. As for the neck and abdomen, clear differences were observed during local cooling, while no significant difference was observed during local warming. We combined the results for the current and the previous study, and characterized regional differences in thermal comfort and thermal preference for the whole-body surface.

Estrogen in the medial preoptic nucleus of the hypothalamus modulates cold responses in female rats.

The present study examined the effect of the central administration of estrogen on responses to the cold. Estrogen or cholesterol was applied locally to the medial preoptic nucleus (MPO) or dorsomedial hypothalamic nucleus (DMH) of the hypothalamus in free-moving ovariectomized rats. Forty-eight hours after the application, rats had 2-h exposure at 10 or 25 degrees C. Body temperature (T(b)) and the tail surface temperature (T(tail)) were continuously measured by telemetry and thermography, respectively. The change of T(b) at 10 degrees C from the 25 degrees C baseline was higher in the estrogen application in the MPO than that in the cholesterol application; however, such difference was not observed in the DMH application. The uncoupling 1 protein mRNA level in the interscapular brown adipose tissue involved in non-shivering thermogenesis was not different between the estrogen and cholesterol applications in the MPO and DMH. T(tail) decreased in the cold, which was greater after the estrogen application in the MPO than after the cholesterol application. These results show that estrogen affects the MPO in female rats, changing T(b) in the cold. Moreover, suppression of heat loss from the tail may be involved in the mechanism.

Thermoregulation in the cold changes depending on the time of day and feeding condition: physiological and anatomical analyses of involved circadian mechanisms.

The circadian rhythm of body temperature (T(b)) is a well-known phenomenon. However, it is unknown how the circadian system including the suprachiasmatic nucleus (SCN) and clock genes affects thermoregulation. Food deprivation in mice induces a greater reduction of T(b) particularly in the light phase. We examined the role of Clock, one of key clock genes and the SCN during induced hypothermia. At 20 degrees C with fasting, mice increased their metabolic heat production in the dark phase and maintained T(b), whereas in the light phase, heat production was less, resulting in hypothermia. Under these conditions, neuronal activity in the SCN, assessed by cFos expression, increased only in the light phase. However, such differences in thermoregulatory and neural responses between the phases in Clock mutant mice were less marked. The neural network between the SCN and paraventricular nucleus appeared to be important in hypothermia. These findings suggest that the circadian system per se is influenced by both the feeding condition and environmental temperature and that it modulates thermoregulation.

Estrogen modulates central and peripheral responses to cold in female rats

The aim of this study was to determine whether estrogen modulates central and peripheral responses to cold in female rats. In ovariectomized female rats with and without administered estrogen [E2 (+) and E2 (−), respectively], the counts of cFos-immunoreactive cells in the medial preoptic nucleus (MPO) and dorsomedial hypothalamic nucleus (DMH) in the hypothalamus were greater in the E2 (+) rats than in the E2 (−) rats at 5°C. Examination of the response of normal female rats to exposure to 5°C at different phases of the estrus cycle revealed that counts of cFos-immunoreactive cells in the MPO, DMH, and posterior hypothalamus and the level of uncoupling protein 1 mRNA in the brown adipose tissues were greater in the proestrus phase than on day 1 of the diestrus phase. This result was linked to the level of plasma estrogen. The body temperature during cold exposure was higher in the E2 (+) rats than in the E2 (−) rats and was also higher in the proestrus phase than on day 1 of the diestrus phase. We conclude that estrogen may affect central and peripheral responses involved in thermoregulation in the cold.

Ghrelin Induces Time-Dependent Modulation of Thermoregulation in the Cold

Fasted mice show torpor-like hypothermia in the cold in their inactive phase. The aim of the present study was to elucidate whether leptin and/or ghrelin are involved in this reaction and to identify its neurophysiological mechanisms. In ob/ob mice, which lack leptin, metabolic heat production (oxygen consumption, Vo2) was suppressed in 20°C cold in both the light and dark phases, resulting in hypothermia. When wild-type mice received a systemic injection of 8 µg ghrelin in the early light phase, followed by a 2-h cold exposure to 10°C, their core body temperature (Tb) decreased by 1.7°C, and they displayed a less marked increase in Vo2 compared with vehicle-injected mice. However, ghrelin injection in the early dark phase resulted in the maintenance of Tb and increased Vo2 in the mice, which was similar to the result observed in the vehicle-injected mice. The number of doubly labeled neurons with cFos and neuropeptide Y (NPY) in the suprachiasmatic nucleus was greater in the light phase in the ghrelin-injected mice, which may suggest that ghrelin activates NPY neurons. On the contrary, in the paraventricular nucleus, the counts became greater only when they were exposed to the cold in the dark phase. These results indicate that ghrelin plays an important role in inducing time-dependent changes in thermoregulation in the cold via hypothalamic pathways. (Author correspondence: tokizawa@aoni.waseda.jp)

Estimation of the core temperature control during ambient temperature changes and the influence of circadian rhythm and metabolic conditions in mice.

It has been speculated that the control of core temperature is modulated by physiological demands. We could not prove the modulation because we did not have a good method to evaluate the control. In the present study, the control of core temperature in mice was assessed by exposing them to various ambient temperatures (Ta), and the influence of circadian rhythm and feeding condition was evaluated. Male ICR mice (n=20) were placed in a box where Ta was increased or decreased from 27°C to 40°C or to -4°C (0.15°C/min) at 0800 and 2000 (daytime and nighttime, respectively). Intra-abdominal temperature (Tcore) was monitored by telemetry. The relationship between Tcore and Ta was assessed. The range of Ta where Tcore was relatively stable (range of normothermia, RNT) and Tcore corresponding to the RNT median (regulated Tcore) were estimated by model analysis. In fed mice, the regression slope within the RNT was smaller in the nighttime than in the daytime (0.02 and 0.06, respectively), and the regulated Tcore was higher in the nighttime than in the daytime (37.5°C and 36.0°C, respectively). In the fasted mice, the slope remained unchanged, and the regulated Tcore decreased in the nighttime (0.05 and 35.9°C, respectively), while the slopes in the daytime became greater (0.13). Without the estimating individual thermoregulatory response such as metabolic heat production and skin vasodilation, the analysis of the Ta-Tcore relationship could describe the character of the core temperature control. The present results show that the character of the system changes depending on time of day and feeding conditions.

Characteristics of activated neurons in the suprachiasmatic nucleus when mice become hypothermic during fasting and cold exposure

Cold defense mechanisms in mice are attenuated in the light phase during fasting, resulting in hypothermia. The present study examined whether specific neurons and areas in the SCN are related to the response. Mice were fasted over 47h or remained fed, during which they were placed at 20 or 27°C for 3h in the light or dark phases. Body temperature (Tb) was monitored. After the exposure, immunoreactive (IR) cells of cFos, arginine vasopressin (AVP), and vasoactive intestinal polypeptide (VIP) in the SCN were assessed. Tb at 20°C during fasting was lower in the light phase than in the dark phase. Both AVP/cFos-IR and VIP/cFos-IR cells increased when mice were at 20°C during fasting in the light phase. Such increase was observed in the central part of the SCN. These responses in the SCN may be related to the hypothermia in the light phase.

Mild hypohydration induced by exercise in the heat attenuates autonomic thermoregulatory responses to the heat, but not thermal pleasantness in humans

Hypohydration caused by exercise in the heat attenuates autonomic thermoregulation such as sweating and skin blood flow in humans. In contrast, it remains unknown if behavioral thermoregulation is modulated during hypohydration. We assume that thermal unpleasantness could drive the behavioral response, and would also be modulated during hypohydration. Nine healthy young men participated in the present study. Body and skin temperatures were monitored. Ratings of thermal sensation and pleasantness were conducted. After approximately 45 min rest at 27 degrees C, they performed 50-min cycling exercise, which was at the level of 40% of heart rate range at 35 degrees C (hypohydration trial) or at the level of 10% of heart rate range at 23 degrees C (control trial), respectively. Subjects returned to the rest at 27 degrees C, and the ambient temperature was then changed from 22 to 38 degrees C. Body weight decreased by 0.9+/-0.1% immediately after exercise in the hypohydration trial and 0.3+/-0.1% in the control trial. In the cold, no significant difference in thermal sensation or pleasantness was observed between trials. There was no significant difference in thermal pleasantness between trials in the heat, although thermal sensation in the heat (32.5-36 degrees C) was significantly lower in the hypohydration trial than in the control trial. In addition, laser Doppler flow of the skin and sweat rate were attenuated in the heat in the hypohydration trial. These results may indicate that mild hypohydration after exercise in the heat has no influence on behavioral responses to the heat.

Hyperosmolality in the plasma modulates behavioral thermoregulation in mice: the quantitative and multilateral assessment using a new experimental system.

We evaluated the effect of plasma hyperosmolality on behavioral thermoregulation in mice, using a new experimental system. The system consisted of Plexiglas box (dimensions: 50×12×19 cm) with five computer-controlled Peltier boards (dimensions: 10×10 cm) at the bottom. Experiments were conducted in two different settings of the system. An operant behavior setting: each board was first set to 39°C, and the right-end board was changed to 20°C for 1 min when a mouse moved to a specific position. A temperature mosaic setting: each board was randomly set to 15°C, 22°C, 28°C, 35°C, or 39°C with a 6-min interval, but each board temperature was different from the others at a given time point. Mice were injected subcutaneous (s.c.) isotonic or hypertonic saline (154 mM (IS group) or 2,500 mM (HS group), 10 ml/kg body wt), and exposed to either setting for 90 min. In the operant setting, the HS group showed fewer operant behavior counts than the IS group (11±5 and 25±4 counts, respectively; P<0.05) with greater increase in body temperature (1.6±0.4°C vs. 0.0±0.2°C, respectively; P<0.05). In the mosaic setting, the HS group selected the board temperature of 35°C more frequently than the other temperatures (P<0.05) with the same increase in body temperature. These results may suggest that plasma hyperosmolality modulates behavioral thermoregulatory response to heat and induce regulated hyperthermia.

Influence of osmotic stress on thermal perception and thermoregulation in heat is different between sedentary and trained men.

Hyperosmolality in extracellular fluid in humans attenuates autonomic thermoregulation in heat, such as sweating and blood flow in the skin. However, exercise training minimizes the attenuation. The aim of the present study was to clarify the influence of hyperosmolality on thermal perception and to assess the training effect of exercise. Ten sedentary (SED) and 10 endurance-trained (TR) healthy young men were infused with 0.9% (normal saline [NS]) or 3% NaCl (hypertonic saline [HS]) for 120min on two separate days. After infusion for 20min, heat stimulus to the skin of the whole body was produced by a gradual increase in hot water-perfused suit temperature (33°C, 36°C, and 39°C), which was first used in the normothermic condition and then in the mild hyperthermic condition (0.5-0.6°C increase in esophageal temperature) and controlled by immersion of the lower legs in a water bath at 34.5°C and 42°C, respectively. Thermal sensation and comfort were rated at the time of each thermal condition. Plasma osmolality increased by ~10mosmL/kg·H2O in the HS trial. In the mild hyperthermic condition, increases in sweat rate and cutaneous vascular conductance were lower in the HS than in the NS trial in both the SED and TR groups (p<0.05). In the SED group, thermal sensation in the mild hyperthermic condition was lower in the HS than in the NS trial (p<0.05); there was no significant difference between the trials in the TR group. These results might indicate that hyperosmolality attenuates thermal sensation with heat and that exercise training eliminates the attenuation.