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

众所周知，金黄地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。在进入阶段，体温（B.T.）降低至接近环境温度，降低的B.T.继续在维护阶段。脑室内（i. c. v.）腺苷（ADO）和ATP给药引起仓鼠体温降低。腺苷Al受体拮抗剂CPT可抑制ADO和ATP引起的体温降低。此外，i. c. v.给药CHA，腺苷A1受体激动剂，降低B.T.几乎达到环境温度。i. c. v.给予β-内啡肽以剂量依赖的方式产生体温降低。DAMGO是一种选择性μ受体激动剂，也降低了B.T.几乎达到环境温度。在入组阶段，给药（i. c. v.）CPT的使用引起了B.T.的上升，但在维持阶段没有。在维持阶段给予纳洛酮， 关于我们 B.T.起义但在入口阶段没有。发病初期下丘脑铝受体数量减少。这些结果表明腺苷调节B、T.而阿片类药物通过Al受体调节B.T.在冬眠唤醒过程中，冬眠仓鼠的体温从6℃迅速上升到37℃。棕色脂肪组织（BAT）产热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在冬眠后唤醒体温过高中的功能联系。脑室内（i. c. v.）TRH的给药在冬眠的仓鼠中产生体温过高，并且冬眠被中断。在急性实验中，直肠和肩胛间BAT（MAT）的温度升高，由i. c. v. TRH。手术切除MAT和/或应用β3受体拮抗剂SR 59230可抑制TRH的兴奋作用。i. c. v.给TRH可引起iBAT中去甲肾上腺素（NE）含量和NE更新率增加。提示中枢TRH系统和外周BAT系统通过交感神经系统在功能上相互联系，在冬眠唤醒过程中起重要作用。在冬眠期间，动物的体温逐渐降低到环境温度。然而，神经元是活的，神经元的传递仍然维持。因此，我们研究冬眠调节物质，如腺苷，阿片，组胺和5-羟色胺，对低温诱导的神经细胞死亡的影响。体外培养的大鼠（非冬眠动物）皮层神经元在18℃下培养12天后，其存活率下降。18℃培养的仓鼠（冬眠动物）皮层神经元活力也明显下降。腺苷和吗啡对低温诱导的大鼠皮层神经元死亡的保护作用。此外，组胺和5-羟色胺也保护培养的神经元。这些结果表明，冬眠调节物质诱导低温冬眠，同时这些物质保护神经元免受低温诱导的细胞凋亡。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