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PubMed1983

Thyroidal iodine and thyroglobulin in hibernating and active Richardson's ground squirrels Spermophilus richardsoni.

Thyroidal iodine, protein and thyroglobulin (TG) were investigated in a hibernator, Spermophilus richardsoni, sampled in the field and from laboratory-held winter colonies. In field animals, thyroidal iodine and protein contents were similar at onset of hibernation and at terminal arousal. Iodine content was increased in laboratory-held animals, a function of alimentary supply, but no differences were observed between hibernators and non-hibernators. Density sucrose gradients showed that approx. 20% of the TG was present as the 12S precursor sub-unit. No variations in the iodine content, nor the iodoamino acid composition of the TG occurred as a function of hibernation.

Amino Acids↗
PubMed1983

Metabolic responses of hibernating golden-mantled ground squirrels Citellus lateralis to lowered environmental temperatures.

1. Hibernating C. lateralis were exposed to lowered ambient temperatures in order to investigate the relationship between hibernation stress and the thermoregulatory responses of the animals. 2. The least hibernation-stress squirrels exhibited a passive decline in metabolic rate until their body temperatures stabilized close to microenvironmental temperature. 3. The most stressed individuals aroused from hibernation in response to the declining ambient temperatures. 4. Intermediately stressed animals demonstrated an initial passive decline in temperature; however, at various temperatures (0.3-6.8 degrees C), this group increased their metabolic rate but did not arouse from hibernation.

Animals↗
PubMed1987

Pancreatic hormones in the nonhibernating and hibernating golden mantled ground squirrel.

The effects of hibernation on pancreatic insulin, glucagon, somatostatin, and pancreatic polypeptide was investigated in the golden mantled ground squirrel (Citellus lateralis). During hibernation, pancreatic organ weight decreased to 57% of the nonhibernating weight. The content of all four pancreatic hormones during hibernation was significantly reduced. The concentrations of insulin, pancreatic polypeptide and somatostatin, but not of glucagon, were significantly reduced during hibernation. The maintenance of the pancreatic glucagon concentration during hibernation may be related to its role in counter-regulation and carbohydrate homeostasis during fasting.

Animals↗
PubMed1988

Non-gonadal mediated effect of photoperiod on hibernation and body weight cycles of the European hamster.

1. Sexually active male European hamsters raised under short photoperiod display high levels of plasma testosterone, high body weight and do not hibernate. 2. Castrated males in May, raised under the same conditions, do not hibernate and do not present the physiological body weight rhythm. 3. Normal and castrated animals under natural conditions enter hibernation and display a normal body weight rhythm. 4. Normal and castrated animals not submitted to the natural succession of long and short days do not enter hibernation. 5. Photoperiod directly controls body weight and hibernation gonadal interactions.

Animals↗
PubMed1992

Comparative analysis of cell replacement in hibernators.

1. Cell renewal in hibernators undergoes seasonal rhythm independent of the hibernation state. 2. We propose that seasonal depression of cell renewal in tissues of hibernators is caused by seasonal involution of thymus in these animals. 3. The latter is known to be involved in the control of cell proliferation. 4. The state of hibernation per se has also an effect on cellular proliferation. 5. It induces the block of cells in the permitotic phase. It is suggested that the blockage of cells in renewing tissues of hibernators under natural deep hypothermia throughout a period of torpidity represents the adaptive reaction of the organism.

Animals↗
PubMed1994

C-fos mRNA increases in the ground squirrel suprachiasmatic nucleus during arousal from hibernation.

During hibernation the body temperature of the golden-mantled ground squirrel, Spermophilus lateralis, may drop below 5 degrees C for a few hours to a week or more. Animals cycle between euthermia and deep hibernation many times over the course of the hibernation season. Expression of the transcription factor c-fos increased in the suprachiasmatic nucleus (SCN) of the hypothalamus, the mammalian circadian clock, during deep hibernation and peaked during the arousal from hibernation. The pattern of increase in c-fos messenger RNA seen in the SCN by in situ hybridization was similar to that seen by Northern blot analysis of total hypothalamic RNA. The induction of c-fos may reflect a wake-up signal, increasing transcription of genes required in the euthermic state.

Animals↗
PubMed1984

Brain gangliosides in hibernating dormice (Glis glis) and cold-exposed laboratory mice.

The concentration of proteins, sialo-glycoproteins and gangliosides and the ganglioside composition of 8 brain regions from normothermic and hibernating fat dormice (Glis glis) and from laboratory mice being acclimated to 6, 22 and 28 degrees C were investigated. During hibernation the concentration of sialo-glycoproteins and gangliosides decreased significantly in brain of dormice; the protein content remained uninfluenced. Cold-exposure of laboratory mice yielded generally a slightly decreased sialo-glycoprotein concentration in brain; the data on ganglioside concentration in the CNS were not uniform. The ganglioside composition of brain of laboratory mice being kept at different environmental temperatures did not show any alterations. The brain gangliosides of hibernating dormice in contrast to their normothermic counterparts are more polar (higher amount of GTlb and GQlb.). Most striking is the complete absence of a distinct ganglioside fraction (O-acetylated-GTlb) during hibernation. Brain gangliosides of normothermic dormice were found to be more sensitive against neuraminidase treatment than those of hibernating animals. The results are discussed with regard to modulatory functions of neuronal gangliosides for the process of synaptic transmission during seasonal adaptation.

Animals↗
PubMed1985

Inhibition of succinate oxidation and K+ transport in mitochondria during hibernation.

Respiration of liver mitochondria of ground squirrels changes with physiological state. The inhibition of respiration at the level of dehydrogenases occurs during hibernation which is spontaneously removed during arousal. The main mechanism causing a decrease in respiration during hibernation seems to be the inhibition of succinate oxidation, induced by oxaloacetic acid. This is evidenced by the removal of the inhibition by glutamic and isocitric acids. A close correlation between the changes of K+ transport in mitochondria and of the physiological state of hibernator is observed. During hibernation the K+ transport rate decreases 3 times and during arousal it increases 1.5-fold in comparison with the active animals. The K+ content in mitochondria of hibernating and active ground squirrels is the same, whereas during arousal it increases 2-fold.

Animals↗
PubMed1993

Opioid binding sites in jerboa (Jaculus orientalis) brain: a biochemical comparative study in the awake-active and induced hibernating states.

1. Using tritiated ligands [3H]DADLE, [3H]DAGO, [3H]EKC and [3H]Bremazocine, we have demonstrated the presence of delta, mu and kappa sites in brain membranes from jerboa (Jaculus orientalis), a desert rodent and a true hibernator. 2. A comparative study was realized in the case of the induced hibernating state, indicating a reduction of binding capacities during the hibernation state. 3. Using radioimmunoassay, the endogenous pentapeptide methionine-enkephalin (Met-enk) was evaluated in different areas of jerboa brain in comparison with the effect of induced hibernation on the level of Met-enk. 4. A thermodynamic analysis of the effect of temperature on the binding of opioids, indicates that the hibernating and the active state are energetically different. delta G degrees, delta H degrees and delta S degrees were calculated. A break of the Van't Hoff plot was observed in the active state at 15 degrees C, indicating a possible transition state of membranous phospholipids and/or proteins. 5. The role of phospholipids was studied, using the effect of phospholipase A2 and membrane reconstitution. Phospholipids play a key role in the opioid binding.

Animals↗
PubMed1992

State-dependent and state-independent effects of thyrotropin-releasing hormone on medial septum neuronal activity in the brain slices of waking and hibernating ground squirrels.

Effects of thyrotropin-releasing hormone on spontaneous activity and responses to medial forebrain bundle stimulation were tested in the units of the medial septum-diagonal band complex in slices taken from the brain of hibernating and waking ground squirrels. Administration of thyrotropin-releasing hormone (0.1 microM) into the flow of incubating medium increased the frequency of spontaneous activity of all the medial septum-diagonal band complex neurons in hibernating ground squirrels and of the majority of neurons in the waking ground squirrels. However, in the septal slices of hibernating ground squirrels this increase was significantly more pronounced. In addition, the neuropeptide slightly increased the frequency of bursts in the majority of cells with rhythmic burst activity. The excitatory influence of thyrotropin-releasing hormone on the units was preserved in conditions of synaptic blockade. In neurons from other structures (lateral septum, medial preoptic area, hippocampus) in the brain slices of both hibernating and waking ground squirrels, thyrotropin-releasing hormone did not usually affect the level of spontaneous discharges. When studying the responses of the medial septum-diagonal band complex neurons to electrical stimulation of medial forebrain bundle it was found that application of thyrotropin-releasing hormone (0.1 microM) led to the disappearance of responses in 50 and 44% of units in the hibernating and waking ground squirrels, respectively; in the rest of the neurons a disturbance of stability and probability of responses was observed. The existence of a modulatory thyrotropin-releasing hormone system which participates post-, and, probably, presynaptically in the regulation of the medial septum-diagonal band complex neuronal activity is suggested. The role of thyrotropin-releasing hormone and of medial septum-diagonal band complex in the neural control of hibernation/euthermic waking cycle is discussed.

Animals↗
PubMed1992

Equithesin: a hibernation-inducing drug?

1. Hibernating insectivore species (hedgehogs) and non-hibernating rodents (guinea pig and rat) were anaesthetized with 'equithesin' (a mixture of chloral hydrate, magnesium sulphate, and pentobarbitone sodium). 2. The physiological responses shown by the hedgehogs were similar to those observed in hedgehogs during a natural or cold-induced hibernation. 3. These responses included a strong reduction in body temperature, heart rate, respiration and oxygen consumption, and brain activity. 4. Such responses to equithesin were not observed in the non-hibernating rodent species. 5. These results suggest that equithesin is a potential tool for hibernation research.

Anesthetics↗
PubMed2005

Up-regulation of a thioredoxin peroxidase-like protein, proliferation-associated gene, in hibernating bats.

Two-dimensional gel electrophoresis was used to assess differential protein expression between euthermic and hibernating states in heart of Myotis lucifugus. A hibernation-induced protein was identified by mass spectrometry as a thioredoxin peroxidase-like protein known as PAG. Western blotting confirmed up-regulation (>2-fold) and RT-PCR also revealed up-regulation (>5-fold) of pag mRNA. Cloning revealed a highly conserved sequence suggesting a conserved function for PAG. Oxidative stress markers, p-IkappaB-alpha (Ser 32) and p-HSP27 (Ser 78/82), were also up-regulated in heart and skeletal muscle during hibernation. Although there are selected increases in gene/protein expression during hibernation, general translation inhibition occurs as part of metabolic rate depression. This was confirmed by elevated levels of the inactive forms of the eIF2alpha (Ser 51) in both heart and skeletal muscle (2- to 5-fold higher than in euthermia) and the eEF2 (Thr 51) in skeletal muscle (a 15-fold increase). This study suggests that hibernators may use up-regulation of specific proteins to counteract oxidative stress.

Adaptation, Physiological↗
PubMed2005

Arousal from hibernation alters contextual learning and memory.

Hibernation is a unique and highly regulated physiological state characterized by profound, albeit periodically reversible, depression in body temperature, metabolism, and consciousness. Hippocampal synapses undergo pronounced remodeling in concert with torpor and arousal. During hibernation, the number of postsynaptic densities, apical dendritic branches, and spine densities decreases substantially in the hippocampus. Upon arousal these parameters increase beyond pre-hibernation levels and peak within 2-3h. By 24h after arousal, dendritic parameters remain elevated but have started to subside, consistent with pruning and differentiation. The present study examined the functional consequences of these natural changes in synaptic structure. Wild-caught Arctic ground squirrels (AGS) were trained in a hippocampal-dependent contextual fear conditioning task at 3h, 24h, or 4 weeks after arousal (warm-adapted euthermic control group). All groups acquired the fear conditioned response similarly on the training day. During a subsequent retention test session, AGS in the 24h group exhibited enhanced expression of contextual fear compared to the other two groups. These data suggest that the morphological and biochemical changes occurring at 24h after arousal from hibernation affect hippocampal-dependent learning and memory. The natural change in synaptic structure during hibernation may provide a unique opportunity to assess the neural substrates underlying cognitive enhancement.

Analysis of Variance↗
PubMed2005

Mitogen-activated protein kinases and selected downstream targets display organ-specific responses in the hibernating ground squirrel.

The responses of mitogen-activated protein kinase (MAPK) family members, including the extracellular signal-regulated kinases (ERKs), the c-jun NH2-terminal kinases (JNKs) and p38MAPK, during mammalian hibernation were analyzed in five organs of Richardson's ground squirrels, Spermophilus richardsonii. Each kinase subfamily responded differently in torpor and each showed organ-specific patterns of response. ERK1/2 activities increased significantly in muscle and brain during hibernation but decreased in kidney and liver. JNK activity rose in four organs (except brain) during hibernation whereas active, phosphorylated p38MAPK increased only in muscle and heart. Activities of ERK-activated kinases also responded to hibernation: MAPKAPK-1 rose in muscle and brain, MAPKAPK-2 decreased in liver and kidney but rose in the other three organs, and p70S6K kinase activity decreased kidney and heart. Transcription factors, c-Jun and CREB, also showed organ-specific responses during torpor. The data suggest key roles for MAPKs in the regulation of the known organ-specific changes in gene expression and protein phosphorylation that define the hibernation phenotype.

Animals↗
PubMed2006

Evidence for a reduced transcriptional state during hibernation in ground squirrels.

During mammalian hibernation, metabolic rate can be reduced to <5% of the euthermic rate as a result of coordinated suppression of multiple energy expensive metabolic processes. Gene transcription is one of these and the present study examines mechanisms of transcriptional control that could contribute to lowering the rate of gene expression in torpor. Histone deacetylases (HDAC) have been linked to gene silencing and measured HDAC activity was 1.82-fold higher in skeletal muscle of hibernating thirteen-lined ground squirrels, Spermophilus tridecemlineatus, compared with euthermic controls. Western blotting also showed that HDAC1 and HDAC4 protein levels were 1.21-and 1.48-fold higher, respectively, in muscle from torpid animals. Histone H3 was also evaluated by Western blotting. Total histone H3 was unchanged but two forms of covalently modified histone H3 that are associated with active transcription (phosphorylated Ser 10 and acetylated Lys 23) were significantly reduced by 38-39% in muscle during hibernation. Finally, RNA polymerase II activity was measured using a PCR-based approach; activity in muscle from hibernating squirrels was only 57% of the euthermic value. These data support an overall decrease in transcriptional activity in skeletal muscle of hibernating animals that is accomplished by multiple molecular mechanisms.

Animals↗
PubMed2004

The effect of soil composition and hydration on the bioavailability and toxicity of cadmium to hibernating juvenile American toads (Bufo americanus).

The soil ecotoxicology literature has focused primarily on a few major taxa, to the neglect of other fossorial organisms such as amphibians. We selected cadmium (Cd) and the American toad (Bufo americanus) as a model contaminant and biological species to assess the impact of soil contamination on amphibian hibernation survival and post-hibernation condition. Soil sand composition (50, 70, 90%) and hydration (100, 150% water holding capacity (WHC)) were manipulated in addition to Cd concentration (0, 56, 165, 483 microg/g) to determine whether these soil properties affect toxicity. Soil Cd concentration significantly reduced survival and locomotor performance, and was correlated negatively with percent mass loss and positively with whole body Cd concentration. Higher sand content resulted in less mass loss and greater Cd uptake. Toads that were hibernated in 50% sand hydrated to 100% WHC had higher survival, less mass loss, and better sprint performance than those hibernated in 50% sand, 150% WHC. This study demonstrates that concentrations of Cd found in soil at highly contaminated sites can be bioaccumulated by hibernating amphibians and may reduce fitness. Differences in microhabitat use may cause species to vary in their exposure and susceptibility to soil contamination. The toxicity of Cd to amphibians could be greater in natural systems where there are multiple stressors and fluctuations in environmental variables.

Animals↗
PubMed2005

Hibernating bears as a model for preventing disuse osteoporosis.

The hibernating bear is an excellent model for disuse osteoporosis in humans because it is a naturally occurring large animal model. Furthermore, bears and humans have similar lower limb skeletal morphology, and bears walk plantigrade like humans. Black bears (Ursus americanus) may not develop disuse osteoporosis during long periods of disuse (i.e. hibernation) because they maintain osteoblastic bone formation during hibernation. As a consequence, bone volume, mineral content, porosity, and strength are not adversely affected by annual periods of disuse. In fact, cortical bone bending strength has been shown to increase with age in hibernating black bears without a significant change in porosity. Other animals require remobilization periods 2-3 times longer than the immobilization period to recover the bone lost during disuse. Our findings support the hypothesis that black bears, which hibernate for as long as 5-7 months annually, have evolved biological mechanisms to mitigate the adverse effects of disuse on bone porosity and strength.

Aging↗
PubMed1998

Suprachiasmatic nucleus: role in circannual body mass and hibernation rhythms of ground squirrels.

Female golden-mantled ground squirrels that sustained complete ablation of the suprachiasmatic nucleus (SCNx) were housed pre- and post-operatively at 23 degrees C and then at 6.5 degrees C for 5-7 yr. SCNx and control animals held at the higher temperature manifested circannual rhythms (CARs) in body mass. In contrast, body mass CARs were not expressed in 50% of SCNx squirrels during cold exposure; rhythm amplitude was reduced to 25-40% of pre-operative values and the interval between successive peaks in body mass fell outside the circannual range. Unlike normal squirrels that hibernate for about 6 months during each circannual cycle, these SCNx squirrels expressed bouts of torpor nearly continuously throughout 2.5 yr of cold exposure. Body mass increases were often observed during hibernation--a phenomenon never observed in control animals. The remaining SCNx squirrels that did not hibernate continuously displayed CARs in body mass within the normal range. The effects of SCN ablation on body mass rhythms presumably are related to disrupted patterns of hibernation, food intake, and metabolism. The SCN, which sustains neural and metabolic activity at low tissue temperatures, may exert greater influence on thermoregulation and metabolism during the hibernation season than at other times of year, thereby accounting for the greater effect of SCN ablation in squirrels maintained at low ambient temperatures.

Animals↗