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、维持期和觉醒期。在进入阶段，仓鼠的体温（B.T.）降低到接近环境温度，降低的B.T.继续处于维护阶段。脑室内 (i.c.v.) 给予腺苷 (ADO) 和 ATP 会导致仓鼠体温过低。 ADO 和 ATP 产生的低温可被腺苷 A1 受体拮抗剂 CPT 抑制。此外，i.c.v.施用 CHA（一种腺苷 A1 受体激动剂）可降低 B.T.接近环境温度。 I.c.v.给予β-内啡肽以剂量依赖性方式产生低温。 DAMGO 是一种选择性 μ 受体激动剂，也可降低 B.T。接近环境温度。在进入阶段，CPT的施用（i.c.v.）引起了B.T.的上升，但在维持阶段则没有。在维持阶段使用纳洛酮会导致 B.T. 升高，但在初始阶段则不会。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。仓鼠在进入阶段通过 Al 受体发挥作用，阿片类药物调节 B.T.冬眠仓鼠在冬眠苏醒期间，体温迅速从6℃升至37℃。棕色脂肪组织（BAT）的产热作用是包括仓鼠在内的啮齿类动物体温过高的重要组成部分。促甲状腺激素释放激素（TRH）通过增加基础代谢产生体温过高。因此，我们研究了中枢TRH和BAT在冬眠唤醒过程中高热中的功能联系。脑室内（i.c.v.）给予TRH会在冬眠仓鼠中产生高热，冬眠被中断。在急性实验中，直肠和肩胛间 BAT (MAT) 的温度因静脉注射而升高。 TRH 的管理。 TRH 的热效应可通过 MAT 手术去神经术和/或使用 SR59230（一种 β3 肾上腺素受体拮抗剂）来抑制。 I.c.v. TRH 给药导致 iBAT 中去甲肾上腺素 (NE) 含量和 NE 周转率增加。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在功能上联系在一起，并且在从冬眠中苏醒期间的高热中发挥着重要作用。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、组胺和血清素对低温诱导的神经细胞死亡的影响。体外培养的大鼠（非冬眠者）皮层神经元在18℃下培养12天后活力下降。培养的仓鼠（冬眠者）皮层神经元的活力也因18℃培养而降低。腺苷和吗啡保护大鼠皮质神经元免受低温引起的细胞死亡。此外，组胺和血清素还可以保护培养的神经元。这些结果表明，冬眠调节物质会诱导冬眠的低温，同时这些物质可以保护神经元免受低温诱导的细胞凋亡。较少的

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