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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The central body temperature (T(b)) regulation system during hibernation was investigated in Syrian hamsters of either sex. Hibernation induced in Syrian hamsters by housing them in a cold room under short day-light/dark cycle was confirmed by marked reductions in the heart rate, T(b) and respiratory rate. The hibernation of hamsters was classified into (i) entrance, (ii) maintenance and (iii) arousal phases according to T(b) changes. In hibernating hamsters, T(b) elevations were phase-selectively elicited by intracerebroventricular (ICV) injection of 8-cyclopenthyltheophylline (CPT; a selective A1-adenosine receptor antagonist) and naloxone (a non-selective opioid receptor antagonist) during the entrance and maintenance phases, respectively. Moreover, a similar T(b) elevation tendency during the maintenance phase was also induced by ICV naloxonazine, (a selective mu1-opioid receptor antagonist), although such was not the case for naltrindole (a selective delta-opioid receptor antagonist) or nor-binaltorphimine (nor-BNI, a selective kappa-opioid receptor antagonist). Furthermore, T(b) elevations in hibernating hamsters were similarly induced with ICV thyrotropin-releasing hormone (TRH) during the entrance and maintenance phases. Furthermore, ICV injection of the anti-TRH antibody ameliorated the T(b) elevations induced by tactile stimulation. These results suggest that activation of the A1-receptor by adenosine is important for the generation of hypothermia in the entrance phase, and that activation of the mu1-opioid receptor by opioid peptides is required for perpetuation of hypothermia in the maintenance phase. In addition, TRH is a key endogenous substance involved in T(b) elevations during the arousal phase of hibernating hamsters.
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PMID:Phase-specific central regulatory systems of hibernation in Syrian hamsters. 1591 Jul 66

The neuroprotective effects of hibernation-regulating substances (HRS) such as adenosine (ADO), opioids, histamine and thyrotropin-releasing hormone (TRH) on low-temperature-induced cell death (LTCD) were examined using primary cultured hamster hippocampal neurons. LTCD was induced when cultures were maintained at <22 degrees C for 7 days. ADO (10-100 microM) protected cultured neurons from LTCD in a dose-dependent manner. The neuroprotective effects of ADO were reversed by both 8-cyclopenthyltheophilline (CPT; A(1) receptor antagonist) and 3,7-dimethyl-1-propargylxanthine (DMPX; A(2) receptor antagonist). Morphine (a non-selective opioid receptor agonist) was also effective in attenuating LTCD at an in vitro dose range of 10-100 muM. The neuroprotective effects of morphine were antagonized by naloxone (a non-selective opioid receptor antagonist). In addition, although [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin (DAMGO; mu-opioid receptor agonist), [D-Pen(2,5)]-enkephalin (DPDPE; delta-opioid receptor agonist) and U-69593 (kappa-opioid receptor agonist) were also effective, LTCD of cultured hippocampal neurons was not affected by TRH. Furthermore, histamine produced hypothermia in Syrian hamsters and protected hippocampal neurons in vitro at 100 microM. The neuroprotective effect of histamine was reversed by pyrilamine (H(1) receptor antagonist). Apoptosis was probably involved in LTCD. These results suggest that ADO protected hippocampal neurons in vitro via its agonistic actions on both A(1) and A(2) receptors, whereas morphine probably elicited its neuroprotective effects via agonistic effects on the mu-, delta- and kappa-opioid receptors. In addition, histamine also protected hippocampal neurons via its agonistic action on the H(1) receptor. Thus, HRS-like adenosine-, opioid- and histamine-like hypothermic actions would most likely induce neuroprotective effects against LTCD in vitro.
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PMID:Neuroprotective effects of hibernation-regulating substances against low-temperature-induced cell death in cultured hamster hippocampal neurons. 1685 91

Torpor during hibernation defines the nadir of mammalian metabolism where whole animal rates of metabolism are decreased to as low as 2% of basal metabolic rate. This capacity to decrease profoundly the metabolic demand of organs and tissues has the potential to translate into novel therapies for the treatment of ischemia associated with stroke, cardiac arrest or trauma where delivery of oxygen and nutrients fails to meet demand. If metabolic demand could be arrested in a regulated way, cell and tissue injury could be attenuated. Metabolic suppression achieved during hibernation is regulated, in part, by the central nervous system through indirect and possibly direct means. In this study, we review recent evidence for mechanisms of central nervous system control of torpor in hibernating rodents including evidence of a permissive, hibernation protein complex, a role for A1 adenosine receptors, mu opiate receptors, glutamate and thyrotropin-releasing hormone. Central sites for regulation of torpor include the hippocampus, hypothalamus and nuclei of the autonomic nervous system. In addition, we discuss evidence that hibernation phenotypes can be translated to non-hibernating species by H(2)S and 3-iodothyronamine with the caveat that the hypothermia, bradycardia, and metabolic suppression induced by these compounds may or may not be identical to mechanisms employed in true hibernation.
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PMID:Central nervous system regulation of mammalian hibernation: implications for metabolic suppression and ischemia tolerance. 1755 47

The ability of mammals to maintain a constant body temperature has proven to be a profound evolutionary advantage, allowing members of this class to thrive in most environments on earth. Intriguingly, some mammals employ bouts of deep hypothermia (torpor) to cope with reduced food supply and harsh climates [1, 2]. During torpor, physiological processes such as respiration, cardiac function, and metabolic rate are severely depressed, yet the neural mechanisms that regulate torpor remain unclear [3]. Hypothalamic responses to energy signals, such as leptin, influence the expression of torpor [4-7]. We show that the orphan receptor GPR50 plays an important role in adaptive thermogenesis and torpor. Unlike wild-type mice, Gpr50(-/-) mice readily enter torpor in response to fasting and 2-deoxyglucose administration. Decreased thermogenesis in Gpr50(-/-) mice is not due to a deficit in brown adipose tissue, the principal site of nonshivering thermogenesis in mice [8]. GPR50 is highly expressed in the hypothalamus of several species, including man [9, 10]. In line with this, altered thermoregulation in Gpr50(-/-) mice is associated with attenuated responses to leptin and a suppression of thyrotropin-releasing hormone. Thus, our findings identify hypothalamic circuits involved in torpor and reveal GPR50 to be a novel component of adaptive thermogenesis in mammals.
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PMID:A role for the melatonin-related receptor GPR50 in leptin signaling, adaptive thermogenesis, and torpor. 2224 Apr 72

We have explored orally effective thyrotropin-releasing hormone (TRH) mimetics, showing oral bioavailability and brain penetration by structure-activity relationship (SAR) study on the basis of in vivo antagonistic activity on reserpine-induced hypothermia in mice. By primary screening of the synthesized TRH mimetics, we found a novel TRH mimetic: l-pyroglutamyl-[3-(thiazol-4-yl)-l-alanyl]-l-prolinamide with a high central nervous system effect compared with TRH as a lead compound. Further SAR optimization studies of this lead compound led to discovery of a novel orally effective TRH mimetic: 1-{N-[(4S,5S)-(5-methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-l-alanyl}-(2R)-2-methylpyrrolidine trihydrate (rovatirelin hydrate), which was selected as a candidate for clinical trials.
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PMID:Discovery of the Orally Effective Thyrotropin-Releasing Hormone Mimetic: 1-{N-[(4S,5S)-(5-Methyl-2-oxooxazolidine-4-yl)carbonyl]-3-(thiazol-4-yl)-l-alanyl}-(2R)-2-methylpyrrolidine Trihydrate (Rovatirelin Hydrate). 3145 10


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