Mechanisms of hibernation and cell protection during hypothermic condition in golden hamster.

众所周知，金仓鼠在寒冷的环境中冬眠。仓鼠的冬眠分为进入期、维持期和唤醒期。在入口阶段，仓鼠的体温下降到接近环境温度，并在维持阶段继续下降。脑室内（i.c.v）给药腺苷（ADO）和ATP可使仓鼠体温过低。经腺苷Al受体拮抗剂CPT抑制的ADO和ATP产生的低温。此外，c.v.给药CHA，一种腺苷Al受体激动剂，将B.T.降低到几乎环境温度。静脉注射β-内啡肽导致体温过低呈剂量依赖性。选择性μ受体激动剂DAMGO也将bt降低到接近环境温度。在进入阶段，CPT的管理（i.c.v）产生了B.T的上升，但在维持阶段没有。维持期给予纳洛酮可使bt升高，而进入期则无升高。进入期下丘脑Al受体数量减少。这些结果表明腺苷调节B，T。而在维持期，阿片通过μ受体调控B.T.。冬眠仓鼠在被唤醒时，体温从6℃迅速上升到37℃。褐色脂肪组织（BAT）的产热是包括仓鼠在内的啮齿类动物热疗的重要组成部分。促甲状腺素释放激素（TRH）通过增加基础代谢产生高热。因此，我们研究了冬眠唤醒时中枢性TRH和BAT在热疗中的功能联系。在冬眠的仓鼠脑室内（i.c.v）施用TRH可产生高热，冬眠被中断。急性实验中，大鼠灌胃TRH后直肠和肩胛间BAT （MAT）温度升高。TRH的高热作用可通过MAT的手术去神经和/或SR59230（一种β3肾上腺素受体拮抗剂）抑制。灌胃TRH引起iBAT去甲肾上腺素（NE）含量和NE周转率升高。这些结果表明，中枢TRH系统和外周BAT系统通过交感神经系统存在功能联系，并在冬眠唤醒时的热疗中发挥重要作用。在冬眠期间，动物的体温降低到环境温度。然而，神经元是活的，神经元传递仍然维持。因此，我们研究了冬眠调节物质，如腺苷、阿片类药物、组胺和血清素，对低温诱导的神经元细胞死亡的影响。体外18℃培养12天后，培养的大鼠（非冬眠）皮层神经元活力下降。在18℃下培养，仓鼠（冬眠）皮层神经元的活力也下降。腺苷和吗啡对低温诱导的大鼠皮层神经元细胞死亡具有保护作用。此外，组胺和血清素对培养的神经元也有保护作用。这些结果表明，冬眠调节物质在诱导低温冬眠的同时，保护神经元免受低温诱导的凋亡细胞死亡。少

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 … More 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