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PubMed1987

Adaptive changes in thermoregulation and their neuropharmacological basis.

Adaptive changes of the thermoregulatory system include morphological and functional modifications. The morphological modifications such as changes in body shape and insulation need time periods of months to years to develop, unless they are genetically fixed and appear seasonally. In general, they are preceded by functional modifications, including changes in capacity of the effector systems and changes in regulatory characteristics, which need much less time to develop. These early changes in regulatory characteristics, which can be defined as deviations in threshold and gain of the thermoregulatory responses, have been described and subdivided into short-term (minutes) and long-term (weeks) modifications. Evidence for the participation of monoaminergic brain stem systems in these modifications has been reviewed. On the basis of recent insights into the organization of the thermoregulatory system, and of evaluation of experimental evidence from electrophysiological, neuropharmacological, and neuroanatomical studies it can be concluded that these systems are involved in adaptive modifications. Receiving information from several sensory systems they seem to deliver additional modulatory signals, which may interfere with the processing of specific thermal information at several sites. Theoretically, the central monoamines may participate in the control of thermal input, in the central integration of thermal signals, and in modification of output signals to thermoregulatory effectors. Best documented is their modulatory action on thermosensitive and thermointegrative hypothalamic neurons. There, the monoamines 5-hydroxytryptamine and noradrenaline act as antagonists, which enhance or diminish the effects of thermal afferents mediated by other transmitters. Moreover, the antagonistic monoaminergic systems are interconnected and can influence each other at the level of lower brain stem. The activity in central monoaminergic systems can also be modified by neurohumoral feedback mechanisms from the periphery. By means of these interrelations the vegetative responses of the organism can be corrected and optimized. These interrelations can explain also some cross-adaptive changes in the thermoregulatory threshold for shivering evoked by nonthermal factors such as food intake or long-distance running.

Adaptation, Physiological↗
PubMed1981

Central adrenoceptors modify hypothalamic thermoregulatory patterns of autonomic activity in conscious rabbits.

In conscious rabbits with indwelling intracisternal (i.c.) catheters i.c. injection of noradrenaline (range 20 - 2000 ng) elicited dose-related cutaneous vasoconstriction of the ear skin vessels and reduction in renal sympathetic vasoconstrictor activity (integrated mass discharge). In addition there was shivering and a rise in the animals "core" temperature, so that the injections of noradrenaline mimicked the normal thermoregulatory pattern of cooling. In 5 other rabbits with implanted hypothalamic thermodes we studied the responses of the ear temperature, renal sympathetic nerve activity and respiration rate to hypothalamic heating and cooling. The animals were studied: (i) under control conditions; (ii) after i.c. administration of noradrenaline: (iii) 24 h after 6-hydroxydopamine (6-OHDA) when there is marked depletion of CNS noradrenergic transmitter stores. After the drugs the temperature-response curves were displaced from control in approximately parallel fashion with little change in gain. Noradrenaline elicited shifts that were directionally opposite to those produced by 6-OHDA, suggesting that the changes in thermoregulatory properties were specific effects of the transmitter. Previous studies also suggest that the site of modulation of the thermoregulatory response is at bulbospinal levels, at least as far as the renal sympathetic response was concerned.

Animals↗
PubMed1982

Hypothalamic regulation of lipid metabolism in the rat: effect of hypothalamic stimulation on lipogenesis.

The rates of fatty acid synthesis and syntheses of other lipids were measured in vivo by determining 3H-incorporation from tritiated water or 14C-incorporation from [U-14C]glucose into white adipose tissues (WAT), brown adipose tissue (BAT) and liver, during electrical stimulation of the ventromedial hypothalamic nucleus (VMH) and the lateral hypothalamic nucleus (LH) of female rats. Electrical stimulation of the VMH markedly increased the rate of fatty acid synthesis and the conversion of glucose to total lipids, glyceride glycerol and phospholipids in interscapular BAT, but not in parametrial or retroperitoneal WAT. Conversely, on VMH stimulation, the syntheses of total lipids, glyceride glycerol and phospholipids from glucose in the liver decreased slightly, though not significantly. Electrical stimulation of the LH had no such effect. Administration of insulin increased the rate of fatty acid synthesis in both brown and white adipose tissues and in the liver. The rate of disappearance of [14C]glucose and the concentration of insulin in the blood were not changed significantly by stimulation of the VMH. These data indicate that electrical stimulation of the VMH, but not the LH, enhances lipogenesis in BAT preferentially through a mechanism not involving insulin, but probably through activation of sympathetic innervation of BAT. The physiological significance of the findings is discussed in relation to hypothalamic function in controlling non-shivering thermogenesis and obesity.

Adipose Tissue↗
PubMed1985

Fluorescent histochemical demonstration of catecholamines in brown adipose tissue from obese (ob/ob) and lean mice acclimated at different temperatures.

Fluorescent histochemistry was used to visualize catecholamines in brown adipose tissue (BAT) of lean and genetically obese mice after they had been acclimated at different temperatures. At all temperatures, strong catecholamine-dependent fluorescence, attributable to the sympathetic innervation, was seen around the blood vessels of BAT from both lean and obese animals. Additionally, catecholamine-dependent fluorescent varicosities, in direct contact with the adipocytes were seen in abundance in lean mice acclimated at 23 degrees, 13 degrees or 4 degrees C and in obese mice acclimated at 13 degrees C. This latter compartment was greatly reduced in lean mice acclimated at 33 degrees C and in obese mice acclimated at 23 degrees and 33 degrees C. Three acute treatments (pretreatment with a monoamine oxidase inhibitor; 24 h food deprivation; and short-term cold exposure followed by short-term warm exposure) all increased the varicose fluorescence associated with adipocytes in obese mice housed at 23 degrees C, which suggests that the low resting level in these animals is attributable, at least in part, to subthreshold concentrations of catecholamines in existing varicosities rather than the absence of sympathetic varicosities per se. These results are in accordance with the results from noradrenaline turnover studies which suggest that the difference in sympathetic nervous system (SNS) activity in BAT from lean and obese (ob/ob) mice is best demonstrated at normal environmental temperatures. The reduced SNS activity in BAT of obese mice (which our studies show to be at the 'cellular' level) is likely to be a major factor in their reduced non-shivering thermogenesis and resultant high efficiency of energy storage as previously suggested by other workers.

Acclimatization↗
PubMed1988

Stage-specific cell-surface antigens of oligodendrocytes in the peripheral nervous system. Expression during development and regeneration and in myelin-deficient mutants.

Monoclonal antibodies to stage-specific cell surface antigens of oligodendrocytes have been used to investigate the expression of antigens 05 through 011 in the peripheral nervous system of the mouse by immunohistology. In the adult sciatic nerve antigens 05 through 09 and 011 were diffusely positive. 010 antigen was not detectable in the peripheral nervous system at any age tested. During development antigens 05, 06 and 07 were first detectable at birth in tracts at the proximal part of the sciatic nerve. At day 2 the whole diameter of the nerve was positive for 05 antigen, while antigens 06 and 07 were detectable only in part of the nerve and antigens 08 and 09 were just about to appear. At day 4 antigen 011 was the last to appear. At day 7 all antigens were strongly detectable throughout the nerve. After transection of adult sciatic nerve expression of antigens 05 through 09 and 011 was studied at the proximal and distal ends of the cut. Three days after transection all antigens were fully detectable in the degenerating myelin and its debris. After 15 days residual debris was still distinctly positive, while Schwann cells in the bands of Bünger were antigen-negative. At approximately two weeks a connecting bridge between proximal and distal ends of the cut nerve had developed, but the 0 antigens were not detectable in this bridge until day 21. At day 42 all antigens were again fully detectable in the regenerating nerve. In hypomyelinating mouse mutants no difference to the normal control littermates was seen in staining pattern and intensity for jimpy and shiverer, while quaking showed an increase in staining intensity for 05 through 08 antigens. In trembler antigens 05, 06 and 07, but not 08, 09 and 011 appeared associated with non-myelin-forming Schwann cells, while the few recognizable myelin-forming Schwann cells expressed all antigens. These observations show that we have characterized 4 new monoclonal antibodies as further reagents to look at developmentally distinct steps in myelination of the peripheral nervous system.

Animals↗
PubMed1994

Myelin localization of a central nervous system ligand for L-selectin.

L-selectin is a lectin-like receptor involved in lymphocyte attachment to lymph node high endothelial venules (HEV). Previously, we showed that L-selectin also participates in the in vitro attachment of lymphocytes to central nervous system (CNS) white matter. Use of an L-selectin chimera demonstrated ligand sites within CNS white matter but not the peripheral nervous system (PNS). Now employing higher resolution mapping, including EM cytochemistry, we localize the ligands to the actual myelin sheaths of CNS neurons. In the shiverer mouse, which lacks compact myelin, ligands are greatly diminished. Comparison of the myelin-associated ligand with the previously characterized HEV-ligands demonstrates a number of differences.

Animals↗
PubMed1995

Behavioural effects of norpethidine, a metabolite of pethidine, in rats.

This study investigated behavioural effects of the toxic pethidine metabolite, norpethidine, in rats and its interactions with reserpine, apomorphine and physostigmine. Following intraperitoneal administration, brain concentrations of norpethidine reached a plateau after 20-40 min and remained elevated for 2 h. In the dose range 0.06-0.18 mmol/kg, norpethidine induced myoclonic jerks, a characteristic splayed posture, and episodes of exaggerated shivering. Forward locomotion, grooming, yawning and rearing were suppressed. Seizures and reverse locomotion occurred occasionally. Administration of reserpine 1 h prior to norpethidine, or of apomorphine or physostigmine 15 min after norpethidine, did not alter the norpethidine-induced behaviours; neither did norpethidine block the effects of apomorphine or physostigmine. The characteristic profile of behaviours induced by norpethidine make this toxicant readily amenable to animal studies. Our results indicate that its mechanism of action is unlikely to involve dopaminergic or cholinergic pathways.

Animals↗
PubMed1983

Effects of cold acclimation on the feeding pattern and energetic metabolism of genetically obese Zucker rats.

1. The feeding pattern, growth rate and energetic metabolism were studied in obese Zucker rats of 5-12 weeks of age kept at ambient temperatures of 22 or 10 degrees C. 2. During this period, the increment in obesity of the 22 degrees C-exposed animal was found to be due to diurnal hyperphagia and not to a lowered resting metabolism. 3. In the 10 degrees C-exposed rat the development of non-shivering thermogenesis associated with a lack of enhancement of food intake leads to prevent the obesity.

Acclimatization↗
PubMed1986

Respiratory adjustments of the unanaesthetized chicken, Gallus domesticus, to elevated metabolism elicited by 2,4-dinitrophenol or cold exposure.

The effects of pharmacologically elevated metabolism on ventilation, gaseous exchange and blood gases were studied in spontaneously breathing unanaesthetized decerebrate chickens using 2,4-dinitrophenol (DNP) injected intravenously in successive single doses of 2.5-5.0 mg/kg. These responses were compared with the cardiorespiratory adjustments to elevated metabolism evoked by shivering in conscious birds. Oxygen consumption increased with cumulative amounts of DNP, reaching 275 +/- 30% of control values at the maximum tolerated dose of 10-15 mg/kg. Increases in ventilation matched the changes in oxygen consumption via increases in both breathing frequency and tidal volume. Arterial blood gases and pH remained unchanged. Exposure to cold (Ta = 2 +/- 2 degrees C) caused oxygen consumption to increase to 185 +/- 21% of control values. Respiratory and cardiovascular adjustments were similar to those evoked by DNP and were comparable to those produced by low intensity treadmill exercise (cf. Gleeson and Brackenbury, 1984).

2,4-Dinitrophenol↗
PubMed1987

Cold acclimation in food-restricted rats.

Food intake, body weight and brown adipose tissue (BAT) mass and composition of rats exposed at 6 degrees C either with food ad libitum or food-restricted were compared with those of rats in the thermoneutral zone, with food ad libitum. Cold acclimation with food ad libitum increases food intake and prevents body weight gains. IBAT (interscapular BAT) increases its mass and changes its composition after 3 weeks of cold exposure. Cold acclimation with food restriction produces a progressive decrease in body weight. IBAT mass increases after 3 weeks but changes in composition occur sooner. It is concluded that the overfeeding that accompanies cold acclimation is not necessary for non-shivering thermogenesis in BAT.

Acclimatization↗
PubMed1988

Thermogenic capabilities of the opossum Monodelphis domestica when warm and cold acclimated: similarities between American and Australian marsupials.

1. Monodelphis domestica is a small marsupial mammal from South America. Its thermogenic abilities in the cold were determined when the opossums were both warm (WA) and cold (CA) acclimated. Maximum heat production of M. domestica was obtained at low temperatures in helium-oxygen. 2. Basal metabolic rate (BMR) in the WA animals was 3.2 W/kg and mean body temperature was 32.6 degrees C at 30 degrees C. These values were lower than those generally reported for marsupials. Nevertheless, these M. domestica showed considerable metabolic expansibility in response to cold. Sustained (summit) metabolism was 8-9 times BMR, while peak metabolism was 11-13 times BMR. These maximum values were equal to, or above, those expected in small placentals. 3. Cold acclimation altered the thermal responses of M. domestica, particularly in warm TaS. However, summit metabolism was not significantly increased; nor did M. domestica show a significant thermogenic response to noradrenaline, which in many small placentals elicits non-shivering thermogenesis. The thermoregulatory responses of this American marsupial were, in most aspects, similar to those of Australian marsupials. This suggests that the considerable thermoregulatory abilities of marsupials are of some antiquity.

Acclimatization↗
PubMed1989

Non-cutaneous peripheral thermosensitivity in the goat (Capra hircus).

1. A 0.2 m2 area of the trunk skin was denervated and its center was externally cooled or warmed, when central body temperature was lowered. 2. When the denervated skin was cooled, the central body temperature, at which shivering occurred, was significantly higher than with warming of the denervated skin. 3. It is concluded that the difference was caused by temperature signals originating from thermoreceptors in tissue layers underneath the denervated skin.

Animals↗
PubMed1991

The effect of experimental overnutrition on nonshivering thermogenesis and obesity in LA/N-cp rats.

1. Groups of congenic adult male lean and obese LA/N-cp rats were fed stock chow or the chow diet plus a cafeteria diet supplement from 4 until 6 months of age. 2. Weight gain, adipose cellularity, and adiposity were greater in obese than in lean rats and all three parameters increased more rapidly in obese than in lean rats when fed the cafeteria-supplemented diet. 3. Resting metabolic rates and basal urinary vanilylmandelic acid excretion were greater in lean than in obese rats, while serum triiodothyronine concentrations were similar in both phenotypes. The cafeteria diet was associated with significant increases in all three metabolic parameters in lean but not in obese rats. 4. The results of this study indicate that the obese phenotype of this strain has an impaired capacity for non-shivering thermogenesis (NST), in association with an enhanced propensity for development of obesity when fed stock or cafeteria diets. Moreover, the impairment in NST involves both sympathetic and thyroidal components, and is likely to be contributory if not causative of obesity in this strain.

Adipose Tissue↗
PubMed1991

Seasonal changes in cation transport in red blood cells of grey squirrel (Sciurus carolinensis) in relation to thermogenesis and cellular adaptation to cold.

1. Unidirectional influx of 42K was measured in red cells of grey squirrels at seasonal intervals over two years. 2. Na/K pump-related (i.e. ouabain-sensitive) K influx at 37 degrees C was maximal in cells collected in January and was more than three times greater than cells collected in summer. Na/K pump activity, maximized by loading the cells with Na, exhibited a similar difference. 3. At 5 degrees C in fresh cells, ouabain-sensitive K influx, expressed as per cent of that at 37 degrees C, was highest in March. In Na-loaded cells it was lowest in summer. 4. Passive "leak" K influx (i.e., the residual influx remaining in presence of ouabain and bumetanide) was highest in October, and declined progressively to the summer months, when it was only 27% of that in October. 5. Cotransport (i.e., bumetanide-sensitive K influx) exhibited the same seasonal pattern as Na/K pump activity in fresh cells. 6. Net gain of Na in cells stored at 5 degrees C for three days in March was less than half of that in January or summer. 7. High transport activity in January may correlate with a requirement for increased non-shivering thermogenesis. However, red cells of grey squirrels exhibit maximum resistance to low temperature in March and at this time resemble the red cells of hibernating mammals.

Acclimatization↗
PubMed1992

Localization, cellular morphology and respiratory capacity of "brown" adipose tissue in newborn reindeer.

1. The localization and cellular morphology of adipose tissue was studied by light, fluorescence and electron microscopy in reindeer between 2 weeks pre partum and 4.5 months post partum during calving, and the subsequent growth period. The respiratory capacity of the adipose tissue was examined in terms of morphometric mitochondrial volume and cytochrome-c oxidase or succinate dehydrogenase activity. 2. Adipose tissue was located at specific anatomical sites in the newborn reindeer (from 0 to 2 days of age). The perirenal-abdominal depot was the largest location (32%) followed by the inter(pre)scapular (18%) and sternal (12%) depots. Internal depot dominated over external or peripheral depots (66-34%). The locations of adipose tissue were largely similar in foetal, newborn and young reindeer. 3. The adipose tissue of the newborn reindeer had all the typical cell morphological characteristics of brown adipose tissue: abundant mitochondria, multilocular fat, high vascularization and a dense spot-like sympathetic innervation between the adipocytes. In the young reindeer, however, it resembled white adipose tissue, being almost totally unilocular with few mitochondria. 4. There was a significant correlation between morphometric mitochondrial volume and cytochrome-c oxidase activity (r = 0.848) in the adipose tissue. Mitochondrial volume, cytochrome-c oxidase and succinate dehydrogenase activity were highest after birth and decreased to almost an undetectable level during the first month. A parallel decrease occurred in the amount of brown adipose tissue from birth (1-2%) to the age of about one month (0.3%). 5. It is concluded that the distinct cell morphological features and high respiratory capacity of the adipose tissue indicate the presence of brown adipose tissue at specific anatomical locations in newborn reindeer. A marked progression towards the characteristics of white adipose tissue then takes place at the same locations during the first month. The results suggest the fundamental significance of brown adipose tissue for non-shivering thermogenesis in newborn reindeer.

Adipose Tissue, Brown↗
PubMed1992

Photoconverted carbocyanine DiI allows direct visualization of transplanted glial cells at the ultrastructural level.

We have used the carbocyanine fluorochrome, DiI, to trace living glial cells (astrocytes, oligodendrocytes and immortalized Schwann cells) after their transplantation into the newborn shiverer and normal mouse brain. DiI fluorescence first detected on vibratome sections, was photoconverted into a stable, non-diffusible and electron-dense diaminobenzidine product. Both fluorescence and precipitate were found in the same cells and were detectable until 60 days after transplantation. At the ultrastructural level, DiI precipitate was contained within cytoplasmic vesicles scattered in the transplanted cell bodies and processes. Photoconversion did not interfere with the cell fine structure or predicted post-transplantation behavior. DiI is thus a suitable marker to trace, at the ultrastructural level, living cells after their transplantation.

Animals↗
PubMed1986

Evidence for the existence of an inner membrane anion channel in mitochondria.

Mitochondria normally exhibit very low electrophoretic permeabilities to physiologically important anions such as chloride, bicarbonate, phosphate, succinate, citrate, etc. Nevertheless, considerable evidence has accumulated which suggests that heart and liver mitochondria contain a specific anion-conducting channel. In this review, a postulated inner membrane anion channel is discussed in the context of other known pathways for anion transport in mitochondria. This anion channel exhibits the following properties. It is anion-selective and inhibited physiologically by protons and magnesium ions. It is inhibited reversibly by quinine and irreversibly by dicyclohexylcarbodiimide. We propose that the inner membrane anion channel is formed by inner membrane proteins and that this pathway is normally latent due to regulation by matrix Mg2+. The physiological role of the anion channel is unknown; however, this pathway is well designed to enable mitochondria to restore their normal volume following pathological swelling. In addition, the inner membrane anion channel provides a potential futile cycle for regulated non-shivering thermogenesis and may be important in controlled energy dissipation.

Animals↗
PubMed1987

Increased oxidative capacity in skeletal muscles from cold-acclimated ducklings: a comparison with rats.

1. The effects of prolonged cold exposure on cytochrome oxidase activity were investigated in skeletal muscles, liver and adipose tissues from cold-acclimated (CA) and control (TN) ducklings and rats. 2. Cold acclimation increased the oxidative capacity of skeletal muscles (+33% in gastrocnemius and +195% in pectoral) and liver (+47%) from CA ducklings, but decreased the oxidative capacity of gastrocnemius muscle (-22%) from CA rats. On the other hand, in these CA rats it increased the oxidative capacity of liver by 88% and, above all, brown adipose tissue by 544%. 3. The significance of these changes due to acclimation to cold in ducklings and rats is discussed. Such an increase in oxidative capacity of CA duckling muscles may explain the non-shivering thermogenesis observed in these birds.

Acclimatization↗