Aguzzi Jacopo, Bullock Nicole M, Tosini Gianluca
Neuroscience Institute and NSF Center for Behavioral Neuroscience, Morehouse School of Medicine, Atlanta, GA 30310-1495, USA.
J Circadian Rhythms. 2006 Apr 4;4:6. doi: 10.1186/1740-3391-4-6.
We have recently reported that spontaneous internal desynchronization between the locomotor activity rhythm and the melatonin rhythm may occur in rats (30% of tested animals) when they are maintained in constant dim red light (LLdim) for 60 days. Previous work has also shown that melatonin plays an important role in the modulation of the circadian rhythms of running wheel activity (Rw) and body temperature (Tb). The aim of the present study was to investigate the effect that desynchronization of the melatonin rhythm may have on the coupling and expression of circadian rhythms in Rw and Tb.
Rats were maintained in a temperature controlled (23-24 degrees C) ventilated lightproof room under LLdim (red dim light 1 microW/cm2 [5 Lux], lower wavelength cutoff at 640 nm). Animals were individually housed in cages equipped with a running wheel and a magnetic sensor system to detect wheel rotation; Tb was monitored by telemetry. Tb and Rw data were recorded in 5-min bins and saved on disk. For each animal, we determined the mesor and the amplitude of the Rw and Tb rhythm using waveform analysis on 7-day segments of the data. After sixty days of LLdim exposure, blood samples (80-100 microM) were collected every 4 hours over a 24-hrs period from the tail artery, and serum melatonin levels were measured by radioimmunoassay.
Twenty-one animals showed clear circadian rhythms Rw and Tb, whereas one animal was arrhythmic. Rw and Tb rhythms were always strictly associated and we did not observe desynchronization between these two rhythms. Plasma melatonin levels showed marked variations among individuals in the peak levels and in the night-to-day ratio. In six rats, the night-to-day ratio was less than 2, whereas in the rat that showed arrhythmicity in Rw and Tb melatonin levels were high and rhythmic with a large night-to-day ratio. In seven animals, serum melatonin levels peaked during the subjective day (from CT0 to CT8), thus suggesting that in these animals the circadian rhythm of serum melatonin desynchronized from the circadian rhythms of Rw and Tb. No significant correlation was observed between the amplitude (or the levels) of the melatonin profile and the amplitude and mesor of the Rw and Tb rhythms.
Our data indicate that the free-running periods (tau) and the amplitude of Rw and Tb were not different between desynchronized and non-desynchronized rats, thus suggesting that the circadian rhythm of serum melatonin plays a marginal role in the regulation of the Rw and Tb rhythms. The present study also supports the notion that in the rat the circadian rhythms of locomotor activity and body temperature are controlled by a single circadian pacemaker.
我们最近报道,当大鼠在持续昏暗红光(LLdim)环境中饲养60天时,其运动活动节律与褪黑素节律之间可能会出现自发的内部不同步现象(30%的受试动物)。先前的研究还表明,褪黑素在调节跑步轮活动(Rw)和体温(Tb)的昼夜节律中起着重要作用。本研究的目的是探讨褪黑素节律不同步对Rw和Tb昼夜节律的耦合及表达可能产生的影响。
将大鼠饲养在温度可控(23 - 24摄氏度)的通风避光房间内,处于LLdim环境(红色昏暗光1微瓦/平方厘米[5勒克斯],波长截止下限为640纳米)。动物单独饲养在配备有跑步轮和用于检测轮子转动的磁传感器系统的笼子里;通过遥测监测Tb。Tb和Rw数据以5分钟的时间间隔记录并保存到磁盘上。对于每只动物,我们使用数据7天时间段的波形分析确定Rw和Tb节律的中值和振幅。在LLdim暴露60天后,在24小时内每隔4小时从尾动脉采集血样(80 - 100微升),并通过放射免疫测定法测量血清褪黑素水平。
21只动物表现出明显的Rw和Tb昼夜节律,而1只动物无节律。Rw和Tb节律始终严格相关,我们未观察到这两种节律之间的不同步现象。血浆褪黑素水平在个体的峰值水平和昼夜比值方面存在显著差异。在6只大鼠中,昼夜比值小于2,而在Rw和Tb表现为无节律的大鼠中,褪黑素水平较高且有节律,昼夜比值较大。在7只动物中,血清褪黑素水平在主观白天(从CT0到CT8)达到峰值,这表明在这些动物中,血清褪黑素的昼夜节律与Rw和Tb的昼夜节律不同步。褪黑素曲线的振幅(或水平)与Rw和Tb节律的振幅及中值之间未观察到显著相关性。
我们的数据表明,不同步和未不同步的大鼠之间,Rw和Tb的自由运行周期(tau)及振幅并无差异,这表明血清褪黑素的昼夜节律在调节Rw和Tb节律中起的作用较小。本研究还支持这样一种观点,即在大鼠中,运动活动和体温的昼夜节律由单个昼夜起搏器控制。