RESTORATION OF CIRCADIAN RHYTHMICITY BY SUPRACHIASMATIC TISSUE GRAFTS

每天的生物节律是由一个生物钟控制的， 下丘脑的视交叉上核。 的结果 几种类型的实验表明， 在SCN中。 SCN的损伤破坏了运动神经元的昼夜节律， 活动、轮跑、皮质醇、褪黑激素、体温等。 SCN包含日常生物钟的进一步证据是 通过观察胎儿SCN组织移植物恢复 SCN损伤的宿主动物的轮运行的昼夜节律。 SCN 移植物恢复了生物钟（间接测量为 自我维持的昼夜节律振荡在车轮运行），以及 生物钟和大脑之间的传出纤维或内分泌联系 更直接地控制输出行为的核。 这样做的目的 项目是调查a）哪些节律（例如体温， 激素、行为）通过SCN移植物恢复，和B）时间过程 的恢复。 先前的实验集中于单个时钟驱动的过程（例如， 轮跑或睡眠-觉醒）以评估SCN移植物的成功。 在 我们的实验是同时测量行为， 生理和神经内分泌节律，以确定a） SCN移植物是否恢复昼夜节律系统的多个输出（例如， 轮跑、脑温和褪黑激素），以及B）时间进程 恢复昼夜节律所需的时间。 胎儿SCN组织 使用杂合的“tau突变仓鼠”作为供体组织， 这种仓鼠品系的昼夜节律周期缩短， 与不完全SCN损伤的昼夜节律不同， 野生型仓鼠 22小时节律的表达可以 作为SCN移植成功的标志。 获得的消息 本实验对研究SCN传出神经的作用具有重要意义 在SCN移植物恢复昼夜节律方面，以及 它们在完整SCN控制昼夜节律中的作用。 我们之前已经证明了收集的可行性， 测定尿中6-硫酸氧褪黑激素的同时昼夜分布 和尿皮质醇。 利用最近开发的 实验装置，在未来一年的昼夜节律在体内 体温、运动活动、尿皮质类固醇和尿 褪黑激素将同时收集在完整的和SCN损伤 仓鼠 我们预计，在未来，这种设备可以用于 测量移植物中昼夜内分泌特征的恢复 受体仓鼠

Daily biological rhythms are controlled by a biological clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The results of several types of experiments indicate the daily biological clock resides within the SCN. Lesions of the SCN abolish circadian rhythms of motor activity, wheel-running, cortisol, melatonin, body temperature, etc. Further evidence that the SCN contains the daily biological clock is provided by the observation that fetal SCN tissue grafts restore circadian rhythms of wheel-running in SCN-lesioned host animals. SCN grafts restore both the circadian clock (measured indirectly as a self-sustained circadian oscillation in wheel-running) as well as efferent fiber or endocrine linkage between the clock, and the brain nuclei which more directly control output behaviors. The purpose of this project is to investigate a) which rhythms (e.g. body temperature, hormonal, behavioral) are restored by SCN grafts and b) the time course of the restoration. Previous experiments focused on a single clock driven process (e.g. wheel-running or sleep-wake) to assess the success of the SCN graft. In our experiments we are simultaneously measuring behavioral, physiological, and neuroendocrine rhythms in order to determine a) whether SCN grafts restore multiple outputs of the circadian system (e.g. wheel-running, brain temperature, and melatonin), and b) the time courses required for circadian rhythm restoration. Fetal SCN tissue of the heterozygous "tau mutant hamster" is used as donor tissue since the clock of this hamster strain has a shortened circadian period that is easily distinguished from the circadian rhythm of incomplete SCN-lesioned, wild-type hamsters. The expression of a twenty-two hour rhythm can then be used as a marker of a successful SCN graft. Knowledge gained from this experiment will be valuable in examining the role of SCN efferents in the restoration of circadian rhythmicity by SCN grafts, as well as their role in the control of circadian rhythmicity by intact SCN. We have previously demonstrated the feasibility of collecting, and assaying simultaneous circadian profiles of urinary 6-sulphatoxymelatonin and urinary cortisol in single hamsters. Using recently developed experimental apparatus, during the coming year circadian rhythms in body temperature, motor activity, urinary corticosteroids, and urinary melatonin will be simultaneously collected in intact and in SCN-lesioned hamsters. We anticipate that in the future, this apparatus can be used to measure the restoration of circadian endocrine profiles in graft recipient hamsters.