| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Akihiro Fukuyama University, Faculty of Pharmacy and pharmaceutical Sciences, Professor, 薬学部, 教授 (70172393)
TAMURA Yutaka Fukuyama University, Faculty of Pharmacy and pharmaceutical Sciences, Assistant Professor, 薬学部, 助教授 (30217202)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
It is known that golden hamster hibernates in cold environment. The hibernation of the hamster is classified into entrance stage, maintenance stage and arousal stage. In entrance stage, the body temperature (B.T.) of hamster lowers to almost environmental temperature, and the lowered B.T. continues in maintenance stage. Intracerebroventricular (i.c.v.) administrations of adenosine (ADO) and ATP produced hypothermia in hamster. The hypothermia produced by ADO and ATP suppressed by CPT, an adenosine Al receptor antagonist. Moreover, i.c.v. administrated CHA, an adenosine Al receptor agonist, lowered the B.T. to almost environmental temperature. I.c.v. administrated β-endorphin produced hypothermia in a dose-dependent manner. DAMGO, a selective μ-receptor agonist, also lowered the B.T. to almost environmental temperature. In entrance stage, administration (i.c.v.) of CPT produced uprise of the B.T., but did not in maintenance stage. Administration of naloxone in maintenance stage produced
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uprise of the B.T., but did not in entrance stage. The Al receptor number of the hypothalamus in entrance stage decreased. These results suggest that adenosine regulates the B,T. of hamster in entrance stage via Al receptor, and opioid regulates B.T. in maintenance stage via μ receptor.
During arousal from hibernation, the body temperature of hibernating hamster rapidly rises from 6℃ to 37℃. Thermogenesis in brown adipose tissue (BAT) is important component for the hyperthermia in the rodents including hamster. Thyrotropin-releasing hormone (TRH) produces the hyperthermia by increase of base metabolism. Therefore, we investigated the functional linkage of central TRH and BAT in the hyperthermia during arousal from hibernation. Intracerebroventricular (i.c.v.) administration of TRH produced hyperthermia in the hibernating hamster, and the hibernation was interrupted. In acute experiment, temperature of rectum and inter scapular BAT (MAT) rose by the i.c.v. administration of TRH. The hyperthrmic effect of TRH was suppressed by surgical denervation of MAT and/or administration of SR59230, a β3 adrenoceptor antagonist. I.c.v. administration of TRH caused increase of norepinephrine (NE) content and NE turnover rate in the iBAT. These results suggest that central TRH system and peripheral BAT system have functionally linked through the sympathetic nervous system, and it is play an important role in the hyperthermia during arousal from hibernation. During hibernation, the body temperature of animal is lowering to the environmental temperature. However, the neuron is alive and neuronal transmission is still maintained. Therefore, we examine the effects of hibernation-regulating substances, such as adenosine, opiate, histamine and serotonin, on neuronal cell death induced by low temperature. The viability of cultured rat (non-hibernator) cortical neuron was decreased by cultivating at 18℃ after 12th day in vitro. The viability of cultured hamster (hibernator) cortical neuron also decreased by cultivating at 18℃. Adenosine and morphine protect rat cortical neurons from cell death induced by low temperature. Moreover, histamine and serotonin also protect cultured neuron. These results suggest that hibernation-regulating substances induce hypothermia for hibernation, at the same time those substances protect the neuron from apoptotic cell death induced by low temperature. Less
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