Thermosensitivity of the preoptic region and the spinal cord in the golden hamster

1. 1.|The effects of thermal stimulation of the preoptic region (POAH) and the spinal cord on non-shivering thermogenesis (NST) and shivering were studied in euthermic golden hamsters.

2. 2.|Shivering intensity is suppressed by heating the POAH but is independent of spinal cord temperature. Therefore, NST in the interscapular brown adipose tissue does not suppress shivering.

3. 3.|NST is inhibited by heating of the POAH as well as of spinal cord. It is discussed that the control of NST by two different central thermosensitive areas is significant for thermoregulation during exercise.

Static response in body temperature regulation of the euthermic warm-acclimated golden hamster (Mesocricetus auratus)

A characteristic feature of the body temperature regulation of euthermic golden hamsters is a great individual variability of body temperature in the thermoneutral zone. Resting values of the total metabolic rate (M) at ambient temperature 30-34 degrees C vary from 5.3 to 8.8 W.kg-1 between individuals, body temperature reaching 33.5-37.7 degrees C (subcutaneous temperature, Ts) and 35.4-39.0 degrees C (hypothalamic temperature, Th). The dependence of metabolic heat production on steady deviations of peripheral and central body temperature from the resting values in nonlinear in general, but the unknown functional relationship delta M = f (delta Th, delta Ts) can be replaced by a single linear regression function of Ts by neglecting the change of central body temperature: delta M = 2.14-2.00. delta Ts. Total body thermosensitivity of the golden hamster determined from steady changes of rectal temperature and metabolic rate after external cooling is -6.8 +/- 1.3 W.kg-1. degrees C-1.     

Ontogeny of cardiac rate regulation and brown fat thermogenesis in golden hamsters (Mesocricetus auratus)

It was shown previously in infant rats (Rattus norvegicus) that the ability to produce heat in the cold using brown adipose tissue (BAT) is closely related to the ability to maintain cardiac rate. When the limits of BAT thermogenesis were exceeded, interscapular temperature (which reflects the temperature of the interscapular BAT depot) and cardiac rate fell together. As an extension of this earlier study, the relation between BAT thermogenesis and cardiac rate was examined here in the golden hamster (Mesocricetus auratus), a species whose young do not exhibit BAT thermogenesis until the end of the 2nd week postpartum. It was found that 3 to 12-day-old hamsters were unable to increase shivering or nonshivering thermogenesis in the cold and exhibited decreases in cardiac rate that proceeded in lock-step with decreases in interscapular temperature. In contrast, as the thermogenic capability of hamsters increased after 12 days of age, cardiac rate was maintained within narrow limits across a wide range of air temperatures. These results support the hypothesis that heat produced by BAT helps to warm the heart and thus aids in the maintenance of cardiac rate during cold exposure. Accepted: 16 August 1997     

Effect of brain stem lesions on hibernation of the hamster (Cricetus cricetus L.)]

Small lesions in the brain stem (including the hypothalamus) of the European hamster were effective with respect to food intake, hibernatory disposition and thermogenic power (oxygen consumption) as well. Hyperphagia was accompanied by depression of hibernation mostly. Moreover, hibernation was hindered by impairment of the thermogenic capacity. Entrance into hibernation depended on the integrity of the middle and caudal hypothalamic areas and the rostral portions of the pons and midbrain. Hyperphagia resulted from destruction of the middle (ventromedial) hypothalamic and caudal hypothalamic areas, including transition structures to the pons. A depression of thermogenesis against cold was observed after destruction of supramammillary and neighbouring mesencephalic areas. Supplementary results: An annual metabolic rhythm characterized by a minimum in december has been established once more. Urethane anesthesia did not abolish cold thermogenesis, despite the development of a slight hypothermia. Poikilothermia resulting from brain stem damage disappeared during a three-day period. Furthermore, diencephalic lesions did not suppress arousal from hibernation significantly.     

Cold adaptive thermogenesis in small mammals from different geographical zones of China

The mechanisms of thermogenesis and thermoregulation were studied in the tree shrew (Tupaia belangeri) and greater vole (Eothenomys miletus) of the subtropical region, and Brandt's vole (Microtus brandti), Mongolian gerbil (Meriones unguiculatus), Daurian ground squirrel (Spermophilus dauricus) and plateau pika (Ochotona curzoniae) of the northern temperate zone. Resting metabolic rate (RMR) and non-shivering thermogenesis (NST) increased significantly in T. belangeri, E. miletus, M. brandti and M. unguiculatus after cold acclimation (4 degrees C) for 4 weeks. In T. belangeri, the increase in RMR and thermogenesis at liver cellular level were responsible for enhancing the capacity of enduring cold stress, and homeothermia was simultaneously extended. Stable body temperature in M. brandti, E. miletus, M. unguiculatus and O. curzoniae was maintained mainly through increase in NST, brown adipose tissue (BAT) mass and its mitochondrial protein content, and the upregulation of uncoupling protein (UCP1) mRNA, as well as enhancement of the activity of cytochrome C oxidase, alpha-glycerophosphate oxidase and T(4) 5'-deiodinase in BAT mitochondria. The RMR in O. curzoniae and euthermic S. dauricus was not changed, while NST significantly increased during cold exposure; the former maintained their stable body temperature and mass, while body temperature in the latter declined by 4.8 degrees C. The serum T(3) concentration or ratio of T(3)/T(4) in all the species was enhanced after cold acclimation. Results indicated that: (1) the adaptive mechanisms of T. belangeri residing in the subtropical region to cold are primarily by increasing RMR and secondly by increasing NST, and the mechanisms of thermogenesis are similar to those in tropical mammals; (2) in small mammals residing in northern regions, the adaptation to cold is chiefly to increase NST; (3) the mechanism of cold-induced thermogenesis in E. miletus residing in subtropical and high mountain regions is similar to that in the north; (4) a low RMR in warm environments and peak RMR and NST in cold environments enabled M. unguiculatus to tolerate a semi-desert climate; (5) O. curzoniae has unusually high RMR and high NST, acting mainly via increasing NST to adapt to extreme cold of the Qinghai-Tibet Plateau; (6) the adaptation of euthermic S. dauricus to cold is due to an increase in NST and a relaxed homeothermia; and lastly (7) the thyroid hormone is involved in the regulation of cold adaptive thermogenesis in all the species studied.     

Role of beta adrenoceptors in metabolic and cardiovascular responses of cold exposed humans

Effect of a nonspecific beta adrenergic blocker — propranolol (40 mg per os) on thermoregulatory responses of cold water immersed (12.5°C) humans was studied. Propranolol attenuates resting and cold induced thermogenesis, rectal temperature, heart rate and systolic blood pressure, but increases production of adrenaline and cortisol. Propranolol has no effect on the threshold body temperature for induction of cold thermogenesis and on central thermosensitivity. The following conclusions are drawn from consideration of the data presented: During the early phase of cooling (20 min after the start of cooling) the thermogenesis mediated by beta adrenergic receptors may cover about 80% of the total metabolic increase induced by cold. After about 30 min of cooling the relative proportion of beta adrenergic thermogenesis starts to decline, reaching 20% of the total cold thermogenesis at the end of cooling.

It can be suggested from consideration of the data that, in man, the beta adrenergic receptors in the heart, blood vessels, adipocytes and muscles participate in mediating effect of cold on cardiovascular and thermoregulatory responses. Furthermore, these data imply that human adrenergic thermogenesis is produced outside of the brown adipose tissue. Thus, physiological mechanisms mediating adrenergic thermogenesis in humans appear to be different from those in small mammals.     

Brown fat temperature decrease by electrical stimulation of in and around retrorubral field in the golden hamster

Electrical stimulation (0.1 ms, 1 mA, 5–50 Hz) of the ventral midbrain of the golden hamster decreased frequency-dependent temperatures of the interscapular brown adipose tissue (IBAT) and rectum. The loci where electrical stimulation evoked continuous decrease in IBAT temperature during the stimulation for 5 min were localized in and around the retrorubral field. Results suggest that tonic inhibitory mechanism on BAT thermogenesis exists in the homologous region of the hamster brain to the rat brain in the previous study.     

温度和高脂食物对黑线仓鼠代谢产热和体脂累积的影响

能量代谢的适应性调节是小型哺乳动物应对环境季节性变化的主要策略之一。为探讨不同温度下动物在代谢产热能量支出与脂肪累积之间的权衡策略,以成年雄性黑线仓鼠为研究对象开展了3 个实验:实验1 将动物驯化于高脂和低脂食物;实验2 将动物暴露于低温(5℃)和暖温(30℃);实验3 将饲喂高脂食物的动物暴露于低温。以食物平衡法测定摄食量、摄入能和消化率,以开放式氧气分析仪测定代谢产热,以索氏抽提法测定脂肪含量。结果发现,取食高脂食物的黑线仓鼠摄食量显著减少,但脂肪累积显著增加;暖温下摄食量显著减少,但体脂含量显著增加,低温下摄食量显著升高,但体脂含量显著减少;饲喂高脂食物的黑线仓鼠在低温下摄入能显著增加,非颤抖性产热增强,但体脂含量显著降低。结果表明高脂食物对黑线仓鼠体脂累积的影响与环境温度有关,低温诱导脂肪动员,暖温促进脂肪贮存;低温下黑线仓鼠增加能量摄入不能完全补偿用于产热的能量支出,导致脂肪动员增加;暖温下代谢产热降低是脂肪累积的主要因素;与能量摄入相比代谢产热的能量支出在体脂累积的适应性变化中发挥更重要的作用。     

Effect of various adaptational temperatures on oxidative capacity of the brown adipose tissue.

Changes in total weight, protein content and activity of cytochrome oxidase have been followed in the brown adipose tissue (BAT) of golden hamsters, white mice and white rats adapted to various temperatures. Important interspecies differences have been detected. The weight and the cytochrome oxidase activity of the BAT of the white mouse changes little under the influence of different adaptational temperatures, whereas in the white rat and in the golden hamster a decrease of adaptational temperature considerably increases the total weight, protein content and cytochrome oxidase activity of this organ. Different adaptational temperatures induce variable effects on the BAT of the golden hamster. Mild cold stimuli favour the accumulation of proteins and of oxidative enzymes, in particular. Severe cold stress also induces growth processes, so that the weight of the BAT increases proportionally to the total body weight of animals. The metabolic capacity of the BAT, measured as total cytochrome oxidase activity, changes substantially with decreasing temperature of adaptation in all species studied, increasing twice, six times and almost twelve times in the mouse, rat and golden hamster, respectively.     

Dynamic effects of acute cooling in body temperature regulation of the euthermic warm-acclimated golden hamster (Mesocricetus auratus)

During the dynamic phase of external cooling of euthermic golden hamsters in the initial period of metabolic response, peripheral body temperature is the decisive control variable determining the level of metabolic heat production. Under these conditions the rate as well as the magnitude of the peripheral body temperature change constitute the effectual input to the controller of body temperature. The apparent sensitivity with which the regulator drives the metabolic response to unit change of the peripheral temperature is in an inverse relation to the rate of peripheral temperature change. This parameter, despite its limited significance can serve as a working index characterising the thermoregulatory system in different groups of experimental animals of the same species providing that the actual conditions of the experiment are comporting.     

Thermal, cardiac and adrenergic responses to repeated local cooling

The aim of this study was to ascertain whether repeated local cooling induces the same or different adaptational responses as repeated whole body cooling. Repeated cooling of the legs (immersion into 12 degrees C water up to the knees for 30 min, 20 times during 4 weeks = local cold adaptation - LCA) attenuated the initial increase in heart rate and blood pressure currently observed in control subjects immersed in cold water up to the knees. After LCA the initial skin temperature decrease tended to be lower, indicating reduced vasoconstriction. Heart rate and systolic blood pressure appeared to be generally lower during rest and during the time course of cooling in LCA humans, when compared to controls. All these changes seem to indicate attenuation of the sympathetic tone. In contrast, the sustained skin temperature in different areas of the body (finger, palm, forearm, thigh, chest) appeared to be generally lower in LCA subjects than in controls (except for temperatures on the forehead). Plasma levels of catecholamines (measured 20 and 40 min after the onset of cooling) were also not influenced by local cold adaptation. Locally cold adapted subjects, when exposed to whole body cold water immersion test, showed no change in the threshold temperature for induction of cold thermogenesis. This indicates that the hypothermic type of cold adaptation, typically occurring after systemic cold adaptation, does not appear after local cold adaptation of the intensity used. It is concluded that in humans the cold adaptation due to repeated local cooling of legs induces different physiological changes than systemic cold adaptation.     

The suprachiasmatic nucleus of the mink (Mustela vison): apparent absence of vasopressin-immunoreactive neurons

The hypothalamic suprachiasmatic nucleus is centrally involved in generation of several circadian rhythms. Neurons of the mammalian suprachiasmatic nucleus express a number of neuropeptides including vasopressin. The suprachiasmatic nucleus of the mink (Mustela vison) is easily distinguished from neighbouring hypothalamic areas and the underlying optic chiasm as a small nucleus containing densely packed parvocellular neurons. A dorsal and ventral subdivision were clearly recognized within the midportion and caudal part of the nuclcus. Using immunohistochemistry, we have identified vasopressin-, neurophysin-, and vasoactive intestinal peptide-immunoreactive neuronal elements in the hypothalamus of the mink. Vasoactive intestinal peptide-immunoreactive neurons can be observed in the ventral aspect of the suprachiasmatic nucleus, but to our surprise, no vasopressin immunoreactive perikarya are found within the suprachiasmatic nucleus, this absence being independent of the experienced annual cycle. The hypothalamic paraventricular and supraoptic nuclei contain large numbers of vasopressin-, neurophysin-and vasoactive intestinal peptide-immunoreactive magnocellular neurons with extensive projections towards the infundibulum and neurohypophysis. A comparative analysis of the distribution of vasopressin-immunoreactive elements in a number of conventional laboratory animals has demonstrated that, in contrast to the rat, golden hamster and Mongolian gerbil, neither vasopressin-containing perikarya in the suprachiasmatic nucleus nor fine calibered immunoreactive fibres entering the adjacent subparaventricular zone are present in the mink. The mink is a photodependent seasonal breeder, and thus vasopressin-immunoreactive neurons in the suprachiasmatic nuclei may not be essential for the photoperiodic regulation of reproduction and seasonal events experienced by this species.     

Physiology and Pharmacology of Hypothermia

Homoiothermic organisms react to hypothermia by shivering and thermogenesis to retain their euthermic state. This reactive homeostatic mechanism recruits a strong sympathetic response, which must be suppressed by anesthesia and adjuvants during induced hypothermia. Below 30° C there is significant neural and organ depression associated with cold narcosis. Cardiac arrhythmias and ventricular fibrillation are grave developments when the core temperature is below 28° C. Proper cardiopulmonary support must be instituted in a patient who has induced or accidental hypothermia at these severely hypothermic levels.Although clinical hypothermia is used to protect the brain and the heart from ischemic insults during an operation, it induces a complex array of physiologic changes in the body that must be appreciated so that optimal care may be provided to a patient.     

Temperature effects on evoked potentials of hippocampal slices from euthermic chipmunks, hamsters and rats

1. Neural activity was recorded in hippocampal slices from euthermic chipmunks, hamsters and rats. 2. While recording the evoked potentials, the temperature of the Ringer's solution bathing the slice was varied by controlling the temperature of an outer chamber jacketing the recording chamber. 3. The temperature just below that at which a population spike could be evoked, Tt, was 10.4 +/- 0.3 degrees C (mean +/- SEM) for chipmunk slices, 14.1 +/- 0.4 degrees C for rat slices and 14.8 +/- 0.4 degrees C for hamster slices. Tt was significantly lower in the chipmunk slices (P<0.01) than in the rat and hamster slices. 4. Data were interpreted as consistent with the hypothesis that chipmunk hippocampal neurons are intrinsically cold resistant.     

Thermoregulatory responses to temperature manipulation of the spinal cord in the marmot

Yellow-bellied marmots (M. flaviventris) acclimated to T_a = 20 °C were implanted with U-shaped polyethylene thermodes in the peridural space of the spinal cord. Decreasing the temperature of the cervical, thoracic, or lumbar areas of the cord increased heart rate, electromyographic activity, and oxygen consumption in the animals. These responses differed qualitatively from those elicited by heating the same cord areas, indicating specificity of the response to the temperature change.Increases in heat production were proportional to the amount of cooling of the cord. The thoracic area was found to be more thermosensitive than the lumbar area. No behavioral or physical thermoregulation was apparent when the spinal cord temperature was changed in these animals.In addition to the conclusion that regulation of spinal cord temperature may be important in the euthermic marmot, it was postulated that the temperature receptors located in the thoracic cord of the marmot may be important in maintaining shivering thermogenesis during arousal from hibernation.     

Increased nonshivering thermogenesis, brown fat cytochrome-c oxidase activity, GDP binding, and uncoupling protein mRNA levels after short daily cold exposure of Phodopus sungorus

In their natural environment, burrowing rodents experience rather fluctuating ambient temperatures and are acutely cold exposed only for short periods outside their burrows. The effect of short daily cold exposure on basal metabolic rate, nonshivering thermogenesis, brown fat thermogenesis, and uncoupling protein mRNA was studied in the Djungarian hamster, Phodopus sungorus. They were kept at 23 degrees C and exposed to 5 degrees C daily either for one 4-h period or twice for 2 h (in 12-h intervals). At the same time control hamsters were kept continuously either at thermoneutrality (23 degrees C) or at 5 degrees C. Two 2-h cold exposures daily were sufficient to increase basal metabolic rate and nonshivering thermogenesis to the same level as continuous cold exposure, whereas one 4-h cold period per day did not result in a significant increase of both parameters. Brown fat thermogenesis (as measured by cytochrome-c oxidase activity and GDP binding to the mitochondrial uncoupling protein) increased to the same extent by both treatments with short daily cold exposure. However, this increase was less than in the chronically cold-exposed hamsters. A similar result was found for uncoupling protein mRNA: both short-term cold-exposed hamsters increased uncoupling protein mRNA levels to a similar extent, but less than after chronic cold treatment. It is concluded that short daily cold exposures are sufficient to cause adaptive increases of the capacity of metabolic heat production as well as brown fat thermogenic properties.     

Changes in plasma cortisol during acute cold exposure in euthermic European hedgehogs: thermoregulatory role of the hypothalamo-pituitary-adrenal axis

Summary During acute cold exposure regulatory heat production of European hedgehogs was significantly increased with a simultaneous rise in the plasma cortisol level. Soon after cold exposure, at the time when standard metabolic rate was measured, the plasma cortisol level was reduced again. This finding indicates a highly reactive hypothalamo-pituitary-adrenal axis in euthermic hedgehogs exposed to a cold environment.Two effects of the adrenocorticostatic agent metopirone ditartrate were observed: (1) A metopirone-induced increase in nonshivering thermogenesis (NST) starting 18 min after application, reaching a maximum after 43 min and disappearing after 90 min (Fig. 1, Table 1). Simultaneously a profound long lasting hyperglycemia was observed (Fig. 2). (2) In contrast to untreated hedgehogs, animals which were given metopirone did not show an increase in the plasma cortisol level, when exposed to cold within 2 to 3 h (Fig. 6).When animals were pretreated with dexamethasone the metopirone-induced NST was suppressed, indicating that the effect of metopirone is mediated by the hypothalamo-pituitary-adrenal system (Fig. 4).The effect of metopirone at doses used in this study was reversible.It is suggested that a combined action of corticosteroids and catecholamines is involved in the control of regulatory heat production.Abbreviations SMR standard metabolic rate - NST nonshivering thermogenesis Supported by the Deutsche Forschungsgemeinschaft Wu 63/5     

Induced rewarming by central stimulation in hypothermic hamsters

Helium-cold hypothermic hamsters, colonic temperature (Tc) 7 to 11 degrees C, injected with acetylcholine (ACH) at a preoptic-anterior hypothalamic (AHPOA) site responded with a rise in colonic temperature while remaining in a cold environmental chamber. The He-Cold hamster does not thermoregulate at these body temperatures. In contrast to central ACH-elicited responses, the injection of alpha and beta adrenergic drugs into the systemic circulation of the He-Cold hamster did not elicit a rise in colonic temperature. The data describe a different animal model of rewarming than has previously been described that is under pharmacologic control by the experimenter. The use of exogenous neurotransmitter provides the potential to understand the mechanisms of thermoregulation in deep experimental hypothermia.     

Metabolic consequences of limited substrate anion permeability in brown fat mitochondria from a hibernator,the golden hamster

Brown fat mitochondria obtained from a hibernator, the golden hamster, were investigated in order to elucidate the significance of membrane permeability for metabolic functioning at different temperatures. The mitochondria were shown to have active permeases for phosphate and pyruvate, but very poorly developed permeases for di- and tricarboxylate substrate anions. This was shown with both osmotic swelling techniques and respiration-driven uptake studies. It was shown that the very limited malate permeation observed was compatible with it being a non-carrier-mediated diffusion process. The role of malate transport in supporting fatty-acid oxidation in vitro as a function of temperature was studied in detail. The results support our earlier suggestion that physiologically pyruvate carboxylase probably functions to generate oxaloacetate when high concentrations of condensing partner are needed during thermogenesis. They may also explain earlier observations that acetate was produced from palmitoyl-carnitine at low temperatures even when malate was present; this is here shown to be due to the limited malate permeability at these low temperatures. Thus, even at the body temperature of the hibernating hamster (4–5°C), brown fat is probably able to combust fatty acids totally.