Decrease In Body Temperature Research Articles

Detection and analysis of autophagy in the American alligator (Alligator mississippiensis).

In response to environmental temperature depression in the fall and winter, American alligators (Alligator mississippiensis) brumate. Brumation is characterized by lethargy, fasting, decreased metabolism, and decreased body temperature. During brumation, alligators will periodically emerge for basking or other encounters when environmental conditions permit. This sporadic activity and lack of nutrient intake may place strain on nutrient reserves. Nutrient scarcity, at the cellular and/or organismal level, promotes autophagy, a well-conserved subcellular catabolic process used to maintain energy homeostasis during periods of metabolic or hypoxic stress. An analysis of the putative alligator autophagy-related proteins has been conducted, and the results will be used to investigate the physiological role of autophagy during the brumation period. Using published genomic data, we have determined that autophagy is highly conserved, and alligator amino acid sequences exhibit a high percentage of identity with human homologs. Transcriptome analysis conducted using liver tissue derived from alligators confirmed the expression of one or more isoforms of each of the 34 autophagy initiation and elongation genes assayed. Five autophagy-related proteins (ATG5, ATG9A, BECN1, ATG16L1, and MAP1-LC3B), with functions spanning the major stages of autophagy, have been detected in alligator liver tissue by western blot analysis. In addition, ATG5 was detected in alligator liver tissue by immunohistochemistry. This is the first characterization of autophagy in crocodylians, and the first description of autophagy-related protein expression in whole blood.

The lactase persistence allele –22018 G/A associated with body mass index in an Asian population

BackgroundA strong association of the –13910 C/T polymorphism with body mass index (BMI) and obesity has been previously reported in Europeans and Chilean goat herders. We aimed to examine the relationship of lactase persistence allele –22018 G/A with BMI and clinical characteristics in an Asian populations. MethodsWe collected 400 samples from seven Iranian ethnic groups, from whom we investigated their lactose tolerance and screened the genetic variants in their lactase gene locus. Height, weight and clinical characteristics were directly measured. WHO classification of BMI was used. ResultsThe results indicated that Increasing BMI increased significantly the risk of blood pressure and fasting glucose and decreased body temperature in the studied population. We showed that the –22018 G/A allele was positively associated with BMI in Iranian and Asian populations (P < 0.05). ConclusionIn conclusion, in Asian population-based 7 major Iranian populations, we found evidence for association of the lactase persistence allele –22018*A with BMI and weight. In the future, meta-analysis of genome-wide association (GWA) studies with larger sample sizes are warranted to confirm our finding.

Neonatal hypothermia

Hypothermia in newborns is a violation of heat metabolism, which is accompanied by a decrease in body temperature below 36.4 °C, manifested by polysystemic disorders of the central nervous system, cardiovascular, respiratory and other systems of the infant's body. Hypothermia occurs with a decrease in the axillary temperature in the newborn lower than 36.4 °C. It can develop rapidly, within 1–2 minutes, with a loss of temperature at a speed of 0.4 °C. It is a serious complication that requires quick and intensive correction; it can lead to irreversible changes, and even death, without the necessary medical care.

Unbalanced thermoregulation in experimental autoimmune encephalitis induced in Lewis rats.

Thermoregulation in patients suffering from multiple sclerosis (MS) is impaired and may result in either increases or decreases in body temperature. We have found that rat experimental autoimmune encephalitis (EAE), being a model of MS, is associated with body temperature disturbances as well. The purpose of the current study was to examine whether the altered body temperature in EAE-induced rats is due to either a deficit in thermoregulation or a controlled change in its set point. Subcutaneous injection of encephalitogenic emulsion into both pads of hind feet of the Lewis rats provoked EAE symptoms. Body temperature (Tb) of 6 rats was measured using biotelemetry system, and ambient temperature (Ta) preferred by 6 rats of another group was analyzed using thermal gradient system. Symptoms of EAE started 11 days postinjection and progressed quickly, culminating in a complete paralysis in rats placed in the gradient, which was associated with behavioural fever (accordingly, selected Ta raised to as much as 32.8±0.5°C vs 27.2±0.6°C in control rats). On the other hand, EAE rats, placed at a constant Ta of 24°C, were able to generate fever (Tb of 37.8±0.1°C) at the start of the illness and then paralysis compromised fever (most likely due to an impairment of thermogenesis), which, surprisingly, resulted in recovery. We conclude that EAE onset in rats is associated with fever and its behavioural supporting leads to aggravation of the autoimmune neurotoxicity.

Body temperature stability observed in the whale sharks, the world's largest fish.

It is generally assumed that the body temperature of large animals is less likely to change due to their large body size, resulting in a high thermal inertia and a smaller surface area to volume ratio. The goal of this study was to investigate the stability of body temperature in large fish using data from field experiments. We measured the muscle temperatures of free-ranging whale sharks (Rhincodon typus), the largest extant fish globally, and investigated their ectothermic physiology and the stability of their body temperatures. The measured muscle temperature of the whale sharks changed substantially more slowly than the water temperature fluctuations associated with vertical movements, and the whole-body heat-transfer coefficients (HTC) of whale sharks estimated using heat-budget models were lower than those of any other fish species measured to date. The heat-budget models also showed that internal heat production does not contribute to changes in muscle temperature. A comparative analysis showed that the HTC at cooling in various fish species including both ectothermic and endothermic species ranging from 10-4 to 103 kg was proportional to body mass-0.63. This allometry was present regardless of whether the fish were ectothermic or endothermic, and was an extension of the relationship observed in previous studies on small fish. Thus, large fish have the advantage of body temperature stability while moving in environments with large temperature variations. Our results suggest that the large body size of whale sharks aids in preventing a decrease in body temperature during deep excursions to more than 1000 m depths without high metabolic costs of producing heat.

Clinical efficiency of clarithromycin-MB in complex therapy of patients with non-hospital pneumonia

Summary: The problem of rational antibiotic therapy of pneumonia is among the most relevant in modern medicine. The aim of the study was to evaluate the clinical efficacy and therapeutic tolerance of parenteral application of clarithromycin in the treatment of patients with non-hospital pneumonia (NHP). Materials and methods. We observed 20 patients: 12 men - (60%), 8 women - (40%), the average age of patients was 46.1 ± 17.6 years. All patients showed clinical symptoms of severe infection of the lower respiratory tract. In 75.0% (15 patients) bilateral lung damage was noted, in 27% (5 patients) - unilateral lung tissue damage. Hemoptysis was observed in 4 (20%) patients. Clarithromycin-MB was included in complex therapy (detoxification, mucolytic drugs, multivitamins, and metabolices) for 6 patients with NHP after 3 days of ineffective starting therapy, 14 patients with emergency received clarithromycin-MB immediately after admission to the hospital. The drug was administered by intravenous drip for 60 minutes at a dose of 500 mg 2 times a day for 7-10 days. Result. The analysis of the obtained results of clarithromycin-MB therapy showed that clinical success was achieved in all patients. The positive dynamics of clinical indicators was noted already on the 3rd day from the beginning of antibiotic therapy with clarithromycin-MB, which was expressed in a decrease in body temperature until the 7th day of treatment, and in almost all patients the temperature returned to normal and only in 1 (5%) patient remained subfebrile. Also, during this period, patients noted a decrease in pain syndrome as well as signs of intoxication. According to the data of X-ray studies on the 10th day of therapy, 6 (30%) patients showed complete disappearance of infiltrative changes in the lungs, in 14 (70%) patients - a significant decrease in their severity. On the 15-24th (average 15.3 ± 1.2) days after the start of therapy signs of inflammatory infiltration in the lungs leveled off on the 15-24th in all patients. Conclusion. Clarithromycin-MB has good therapeutic tolerance, allows maintaining the required concentration in the focus of inflammation because of dosage regimen also affects the clinical and bacteriological effectiveness of therapy.

Duration of thermal support for preventing hypothermia induced by anesthesia with medetomidine-midazolam-butorphanol in mice.

Hypothermia during anesthetic events is a common adverse effect of anesthesia in laboratory animals. In particular, small rodents such as mice is susceptible to hypothermia during anesthetic events. Therefore, the animals will need additional thermal support by external heating devices during and after anesthesia. In general, the time of recovery from anesthesia is typically longer in case of injectable anesthesia rather than inhalant anesthesia. However, the durations of thermal support have been almost limited to 1 hr from administration of anesthesia in general. Our study objectives are two-fold: 1) to compare the levels of hypothermia induced by injectable anesthesia with medetomidine-midazolam-butorphanol (MMB) and inhalant anesthesia with isoflurane (ISO); 2) to find the adequate durations of thermal support for preventing hypothermia induced by their anesthesia in mice. Adult male ICR mice were anesthetized during 40 min without and with the thermal support for 1 (both anesthetic groups), 2, 3, and 5 hr (in MMB group). Without thermal support, the decrease of body temperature in MMB group were more severe than that in ISO group. The durations of thermal support completely prevented hypothermia at 5 hr-support in MMB group and that at 1 hr-support in ISO group. However, the other short durations did not prevent hypothermia at 1, 2 and 3 hr-support in MMB group. These results suggest that the mice should be received thermal support over 5 hr after injection of MMB anesthesia to prevent hypothermia.

Does the New Zealand rockwren (Xenicus gilviventris) hibernate?

In this study, we examined the thermal physiology of the endangered New Zealand rockwren (Xenicus gilviventris), a member of the Acanthisittidae, a family unique to New Zealand. This family, derived from Gondwana, is thought to be the sister taxon to all other passerines. Rockwrens permanently reside above the climatic timberline at altitudes from 1000 to 2900 m in the mountains of South Island. They feed on invertebrates and in winter face ambient temperatures far below freezing and deep deposits of snow. Their body temperature and rate of metabolism are highly variable. The rockwrens in our study regulated their body temperature at ca. 36.4°C, which in one individual decreased to 33.1°C at an ambient temperature of 9.4°C; its rate of metabolism decreased by 30% and its body temperature then spontaneously returned to 36°C. The rate of metabolism in a second individual twice decreased by 35%, nearly to the basal rate expected from its mass without a decrease in body temperature. The New Zealand rockwren's food habits, entrance into torpor and continuous residence in a thermally demanding environment suggest that it may hibernate. However, for that conclusion to be accepted, evidence of its use of torpor for extended periods is required. Acanthisittids are distinguished from other passerines by the combination of their permanent temperate distribution, thermal flexibility and a propensity to evolve a flightless condition. These characteristics may principally reflect their geographical isolation in a temperate environment isolated from Gondwana for 82million years in the absence of mammalian predators.

Hypothermia during long-term use of fluoxetine: a case report

Selective serotonin reuptake inhibitors are commonly used molecules in the treatment of psychiatric disorders. Among clinicians, fluoxetine is an antidepressant that is considered safe and preferred in major depressive disor-der. Many short-term and long-term effects of fluoxetine have been reported. Nausea, insomnia, headache, tre-mor, anxiety, dizziness, dry mouth, sweating, constipation, diarrhea are common and possible side effects during fluoxetine treatment. It is suggested that these side effects usually occur at the beginning of treatment and disap-pear spontaneously in the future. Hypothermia due to the use of fluoxetine has been demonstrated in animal ex-periments studies. In experimental studies, the effects of other pharmacological molecules on thermoregulation and the effect of fluoxetine on these molecules, increasing or decreasing body temperature are prominent. Clinical applications of fluoxetine for thermoregulation are directed to the treatment of female patients who develop post-menopausal fever flashes. No study reported hypothermia as a side effect after fluoxetine use in any psychiatric disorder. In this case, we present a patient who developed hypothermia following long-term use of fluoxetine.

Hypobaric hypoxia preconditioning protects against hypothalamic neuron apoptosis in heat-exposed rats by reversing hypothalamic overexpression of matrix metalloproteinase-9 and ischemia.

Background: Hypoxia-inducible factor-1α (HIF-1α), heat shock protein-72 (HSP-72), hemeoxygenase-1 (HO-1), and matrix metalloproteinase-9 (MMP-9) have been identified as potential therapeutic targets in the brain for cerebral ischemia. To elucidate their underlying mechanisms, we first aimed to ascertain whether these proteins participate in the pathogenesis of heat-induced ischemic damage to the hypothalamus of rats. Second, we investigated whether hypobaric hypoxia preconditioning (HHP) attenuates heat-induced hypothalamic ischemic/hypoxic injury by modulating these proteins in situ.Methods: Anesthetized rats treated with or without HHP were subjected to heat stress. Hypothalamic ischemic/hypoxic damage was evaluated by measuring hypothalamic levels of cerebral blood flow (CBF), partial oxygen pressure (PO2), and hypothalamic temperature via an implanted probe. Hypothalamic apoptotic neurons were counted by measuring the number of NeuN/caspase-3/DAPI triple-stained cells. Hypothalamic protein expression of HIF-1α, HSP-72, HO-1, and MMP-9 was determined biochemically.Results: Before the start of the thermal experiments, rats were subjected to 5 hours of HHP (0.66 ATA or 18.3% O2) daily for 5 consecutive days per week for 2 weeks, which led to significant loss of body weight, reduced brown adipose tissue (BAT) wet weight and decreased body temperature. The animals were then subjected to thermal studies. Twenty minutes after heat stress, heat-exposed rats not treated with HHP displayed significantly higher core and hypothalamic temperatures, hypothalamic MMP-9 levels, and numbers of hypothalamic apoptotic neurons but significantly lower mean blood pressure, hypothalamic blood flow, and PO2 values than control rats not exposed to heat. In heat-exposed rats, HHP significantly increased the hypothalamic levels of HIF-1α, HSP-72, and HO-1 but significantly alleviated body and hypothalamic hyperthermia, hypotension, hypothalamic ischemia, hypoxia, neuronal apoptosis and degeneration.Conclusions: HHP may protect against hypothalamic ischemic/hypoxic injury and overexpression of MMP-9 by upregulating the hypothalamic expression of HIF-1α, HSP-72, and HO-1 in rats subjected to heatstroke.

Design and Implementation of Hypothermia Symptoms Early Detection With Smart Jacket Based on Wireless Body Area Network

Hypothermia is a state where the body cannot balance the body heat due to excessive cold temperature pressure so that there will be loss of heat in the body. The result will be a quickly decreasing body temperature. A condition where a body temperature is less than 35°C and that it is accompanied by a decrease in consciousness may cause a death threat. Hypothermia is more common when climbers perform activities in cold temperatures and strong winds, and when they wear wet clothes. It is not easy for a mountain climber to find out his own body temperature as well as that of his friends and to determine whether the body temperature is safe or affected by hypothermia symptoms. Therefore, this research formed a device to detect hypothermia. It consists of temperature sensor, pulse sensor, and accompanied by heating elements based on wireless body area network (WBAN). This device will connect to the user’s smartphone by using Bluetooth, so the user can see the condition of his body, adjust the temperature of the heating element, and make a group of climbers. The experiment result shows that the device can detect hypothermia symptoms and inform these symptoms to the users and groups of mountaineers in WBAN area, and the climbers can be more vigilant in responding to hypothermia so that mortality cases caused by hypothermia can be minimized.

CLINICAL ASSESSMENT OF THE EFFECTIVENESS APPLICATION "BIOCERULIN" IN THE COMPLEX TREATMENT OF THE PATIENTS WITH ONTOGENIC FLAGMONS OF THE MAXILLOFACIAL AREA

Treatment of odontogenic phlegmon of the maxillofacial region remains an urgent problem of surgical dentistry due to the steady increase in their frequency, tendency to generalize the process and adverse effects. In this regard, there is a constant search for ways to improve the effectiveness of treatment of patients with odontogenic phlegmons of maxillofacial region. New technologies of drug treatment of this pathology are developed and put into practice.&#x0D; In recent years the attention of researchers in various conditions accompanied by the development of oxidative stress began to attract drugs that have antioxidant action, as it became known that the excess of reactive oxygen species in the regenerating wounds in the hearth of purulent inflammation affects the course of the course, wound healing. Interest in the treatment of various pathological conditions of the body is caused by the domestic antioxidant multifunctional enzyme "Bioceruline" which is composed of copper.&#x0D; In this regard, the purpose of our study was to evaluate the effectiveness of the use of "Biocerulin" in the complex treatment of patients with odontogenic phlegmon of maxillofacial region.&#x0D; The object of the clinical study was 45 patients with odontogenic phlegmons of the maxillofacial region from 18 to 55 years old, who were treated in the maxillofacial department of PU "Poltava M.V. Sklifosovskyi regional clinical hospital PRC». All patients were without somatic pathology in compensated clinical condition. Immediately after hospitalization, patients underwent an emergency opening of purulent lesion, revision and adequate drainage of the affected cellular spaces, removal of the "causal" tooth. The extent of surgery and the choice of optimal access depended on the location and prevalence of phlegmon. Depending on the treatment, patients were divided into comparison groups (22 patients) and the main group (23 patients). The traditional therapy was used in the comparison group. "Biocerulin"was prescribed for the patients of the main group in addition to the traditional therapy.&#x0D; Analysis of obtained data in the treatment of patients with phlegmon revealed that both groups of patients had clear differences in the clinical course of purulent-inflammatory process. On the 2nd day after the opening of the phlegmon theweakness, headache, and sleep disorders were noted in the most of the patients of the comparison group who received traditional therapy. Pain with varying degrees of intensity was present in all patients. Improvement of the general condition of patients of this group was noted not earlier than 3-5 days after surgery. The improvement of the general condition and reduction of pain, normalization or decrease in body temperature, the beginning of restoration of function of the jaw apparatuswere notedin patients of the main group on the background of the introduction of "Bioceruline" already on the 2-3rd day after surgery.&#x0D; Thus, on the basis of the conducted researches it is possible to conclude that the basic (traditional) conservative therapeutic measures used for patients of the comparison group are not effective enough for the relief of the local and general inflammatory process, which caused the prolonged nature of organ-specific and functional rehabilitation of patients as a whole. The use of "Bioceruline" in complex therapy of patients with odontogenicphlegmons of the maxillofacial regionprovides rapid and intensive recovery of the general condition of patients and accelerates reparative processes in the wound and shortens the treatment time via 1.4 bed-days.

Effects of Tempol in Lipopolysaccharide-Induced Liver Injury

Objective: Sepsis leads to conditions such as inflammatory and anti-inflammatory process, circulatory abnormalities, cellular and humoral reactions. Endotoxin-induced oxidative stress causes injury in the liver. The aim of this study was to evaluate the effects of a radical scavenger Tempol in lipopolysaccharide (LPS)-induced liver injury in rats. Materials and Methods: Male Wistar rats were divided into four groups: Control, LPS (15 mg/kg), LPS + Tempol group (100 mg/kg Tempol, three hours after LPS administration) and Tempol (100 mg/kg). Blood glucose and body temperature were measured during the experiment. Superoxide dismutase (SOD), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and C-reactive protein (CRP) levels were measured in plasma or liver tissue. Furthermore, histopathological changes and myeloperoxidase-stained leukocytes infiltration were assessed in liver tissue. Results: LPS caused tissue damage and leukocytes infiltration, increased AST, ALT and CRP levels, and decreased body temperature, blood glucose and SOD levels. Tempol reduced AST and ALT levels and increased SOD levels. Tempol did not prevent tissue damage, leukocytes infiltration and increment of CRP levels. There were no changes in body temperature and blood glucose levels. Conclusion: The present study suggests that tempol may have antioxidant properties in LPS-induced liver injury. These results may contribute to a better understanding of the role of tempol and basic mechanisms of underlying oxidative stressrelated liver injury for further investigations.

Activation of Kappa Opioid Receptor Regulates the Hypothermic Response to Calorie Restriction and Limits Body Weight Loss.

Mammals maintain a nearly constant core body temperature (Tb) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering Tb [1-6]. This adaptive response conserves energy, limiting the loss of body weight due to low calorie intake [7-10]. Here we show that this response is regulated by the kappa opioid receptor (KOR). CR is associated with increased hypothalamic levels of the endogenous opioid Leu-enkephalin, which is derived from the KOR agonist precursor dynorphin [11]. Pharmacological inhibition of KOR, but not of the delta or the mu opioid receptor subtypes, fully blocked CR-induced hypothermia and increased weight loss during CR independent of calorie intake. Similar results were seen with DIO mice subjected to CR. In contrast, inhibiting KOR did not change Tb in animals fed ad libitum (AL). Chemogenetic inhibition of KOR neurons in the hypothalamic preoptic area reduced the CR-induced hypothermia, whereas chemogenetic activation of prodynorphin-expressing neurons in the arcuate or the parabrachial nucleus lowered Tb. These data indicate that KOR signaling is a pivotal regulator of energy homeostasis and can affect body weight during dieting by modulating Tb and energy expenditure.

Impact of rewarming rate on the mortality of patients with accidental hypothermia: analysis of data from the J-Point registry

BackgroundAccidental hypothermia (AH) is defined as an involuntary decrease in core body temperature to < 35 °C. The management of AH has been progressing over the last few decades, and numerous techniques for rewarming have been validated. However, little is known about the association between rewarming rate (RR) and mortality in patients with AH.MethodThis was a multicentre chart review study of patients with AH visiting the emergency department of 12 institutions in Japan from April 2011 to March 2016 (Japanese accidental hypothermia network registry, J-Point registry). We retrospectively registered patients using the International Classification of Diseases, Tenth Revision code T68: ‘hypothermia’. We excluded patients whose body temperatures were unknown or ≥ 35 °C, who could not be rewarmed, whose rewarmed temperature or rewarming time was unknown, those aged < 18 years, or who or whose family members had refused to join the registry. RR was calculated based on the body temperature on arrival at the hospital, time of arrival at the hospital, the documented temperature during rewarming, and time of the temperature documentation. RR was classified into the following five groups: ≥2.0 °C/h, 1.5–< 2.0 °C/h, 1.0–< 1.5 °C/h, 0.5–< 1.0 °C/h, and < 0.5 °C/h. The primary outcome of this study was in-hospital mortality. The association between RR and in-hospital mortality was evaluated using multivariate logistic regression analysis.ResultDuring the study, 572 patients were registered in the J-Point registry, and 481 patients were included in the analysis. The median body temperature on arrival to the hospital was 30.7 °C (interquartile range [IQR], 28.2 °C–32.4 °C), and the median RR was 0.85 °C/h (IQR, 0.53 °C/h–1.31 °C/h). The in-hospital mortality rates were 19.3% (11/57), 11.1% (4/36), 14.4% (15/104), 20.1% (35/175), and 34.9% (38/109) in the ≥2.0 °C/h, 1.5–< 2.0 °C/h, 1.0–< 1.5 °C/h, 0.5–< 1.0 °C/h, and < 0.5 °C/h groups, respectively. Multivariate regression analysis revealed that in-hospital mortality rate increased with each 0.5 °C/h decrease in RR (adjusted odds ratio, 1.49; 95% confidence interval, 1.15–1.94; Ptrend < 0.01).ConclusionThis study showed that slower RR is independently associated with in-hospital mortality.

Effective Field Immobilization of Andean Fox (Lycalopex culpaeus) with Ketamine-Dexmedetomidine and Antagonism with Atipamezole

A combination (mean±SD) of ketamine (4.0±1.0 mg/kg in juveniles and 3.0±0.4 in adults) and dexmedetomidine (0.055±0.01 and 0.049±0.01, respectively), reversed with atipamezole (at 10 mg/mg of dexmedetomidine), was assessed in 57 Andean foxes (Lycalopex culpaeus) in field conditions. Induction times in juveniles and adults were 4.6±3.9 min and 4.3±2.4 min, respectively. Immobilization was smooth and safe, and lasted 50±8 min in juveniles and 50±10 min in adults. Full recovery was recorded at 40±29 min in juveniles and 37±23 min in adults after atipamezole administration. Drug dose, season, body temperature, and fox sex and body condition were not related to variations in induction and recovery times, body temperature, heart rate, respiratory rate, or hemoglobin oxygen saturation. No side effects were observed other than a slight but significant decrease in mean body temperature during the procedure. This combination allowed carrying out all the typical procedures of a research project, including the collection of several biologic samples.

The Golgi Apparatus of Neocortical Glial Cells During Hibernation in the Syrian Hamster.

Hibernating mammals undergo torpor periods characterized by a general decrease in body temperature, metabolic rate, and brain activity accompanied by complex adaptive brain changes that appear to protect the brain from extreme conditions of hypoxia and low temperatures. These processes are accompanied by morphological and neurochemical changes in the brain including those in cortical neurons such as the fragmentation and reduction of the Golgi apparatus (GA), which both reverse a few hours after arousal from the torpor state. In the present study, we characterized – by immunofluorescence and confocal microscopy – the GA of cortical astrocytes, oligodendrocytes, and microglial cells in the Syrian hamster, which is a facultative hibernator. We also show that after artificial induction of hibernation, in addition to neurons, the GA of glia in the Syrian hamster undergoes important structural changes, as well as modifications in the intensity of immunostaining and distribution patterns of Golgi structural proteins at different stages of the hibernation cycle.

Nicotinic acid promotes sleep through prostaglandin synthesis in mice

Nicotinic acid has been used for decades for its antiatherogenic properties in humans. Its actions on lipid metabolism intersect with multiple sleep regulatory mechanisms, but its effects on sleep have never been documented. For the first time, we investigated the effects of acute systemic administration of nicotinic acid on sleep in mice. Intraperitoneal and oral gavage administration of nicotinic acid elicited robust increases in non-rapid-eye movement sleep (NREMS) and decreases in body temperature, energy expenditure and food intake. Preventing hypothermia did not affect its sleep-inducing actions suggesting that altered sleep is not secondary to decreased body temperature. Systemic administration of nicotinamide, a conversion product of nicotinic acid, did not affect sleep amounts and body temperature, indicating that it is not nicotinamide that underlies these actions. Systemic administration of monomethyl fumarate, another agonist of the nicotinic acid receptor GPR109A, fully recapitulated the somnogenic and thermoregulatory effects of nicotinic acid suggesting that they are mediated by the GPR109A receptor. The cyclooxygenase inhibitor indomethacin completely abolished the effects of nicotinic acid indicating that prostaglandins play a key role in mediating the sleep and thermoregulatory responses of nicotinic acid.

Angiogenic signaling in the lungs of a metabolically suppressed hibernating mammal (Ictidomys tridecemlineatus).

To conserve energy in times of limited resource availability, particularly during cold winters, hibernators suppress even the most basic of physiologic processes. Breathing rates decrease from 40 breaths/minute to less than 1 breath/min as they decrease body temperature from 37 °C to ambient. Nevertheless, after months of hibernation, these incredible mammals emerge from torpor unscathed. This study was conducted to better understand the protective and possibly anti-inflammatory adaptations that hibernator lungs may use to prevent damage associated with entering and emerging from natural torpor. We postulated that the differential protein expression of soluble protein receptors (decoy receptors that sequester soluble ligands to inhibit signal transduction) would help identify inhibited inflammatory signaling pathways in metabolically suppressed lungs. Instead, the only two soluble receptors that responded to torpor were sVEGFR1 and sVEGFR2, two receptors whose full-length forms are bound by VEGF-A to regulate endothelial cell function and angiogenesis. Decreased sVEGFR1/2 correlated with increased total VEGFR2 protein levels. Maintained or increased levels of key γ-secretase subunits suggested that decreased sVEGFR1/2 protein levels were not due to decreased levels of intramembrane cleavage complex subunits. VEGF-A protein levels did not change, suggesting that hibernators may regulate VEGFR1/2 signaling at the level of the receptor instead of increasing relative ligand abundance. A panel of angiogenic factors used to identify biomarkers of angiogenesis showed a decrease in FGF-1 and an increase in BMP-9. Torpid lungs may use VEGF and BMP-9 signaling to balance angiogenesis and vascular stability, possibly through the activation of SMAD signaling for adaptive tissue remodeling.

3-Iodothyronamine Induces Diverse Signaling Effects at Different Aminergic and Non-Aminergic G-Protein Coupled Receptors

The thyroid hormone metabolite 3-iodothyronamine (3-T1AM) exerts diverse physiological reactions such as a decrease of body temperature, and negative inotropic and chronotropic effects. This observed pleomorphic effect in physiology can be barely explained by interaction with only one target protein such as the trace-amine receptor 1 (TAAR1), a class A G-protein coupled receptor (GPCR). Moreover, Taar1 knock-out mice still react to 3-T1AM through physiological responses with a rapid decrease in body temperature. These facts propelled our group and others to search for further targets for this molecule.The group of TAARs evolved early in evolution and, according to sequence similarities, they are closely related to adrenoceptors and other aminergic receptors. Therefore, several of these receptors were characterized by their potential to interplay with 3-T1AM. Indeed, 3-T1AM acts as a positive allosteric modulator on the beta2-adrenoceptor (ADRB2) and as a biased agonist on the serotonin receptor 1B (5HT1b) and the alpha2-adrenoceptor (ADRA2A). In addition, 3-T1AM was reported to be a weak antagonist at a non-aminergic muscarinic receptor (M3).These findings impressively reflect that such trace amines can unselectively and simultaneously function at different receptors expressed by one cell or at different tissues. In conclusion, the role of 3-T1AM is hypothesized to concert the fine-tuning of specific cell reactions by the accentuation of certain pathways dependent on distinct receptors. 3-T1AM acts as a regulator of signals by blocking, modulating, or inducing simultaneously distinct intracellular signaling cascades via different GPCRs.