| Research Abstract |
The aim of the present study is to investigate the properties of human circadian signal transmission and influence of aging on the humoral/neuronal signal transmission and their reciprocal phase relationship. We firstly established measuring method for expression analysis of 10 circadian clock genes including hPer1, hPer2, hPer3, Clock, BMAL1, Timeless, Cry1, Cry2, Dec1, Dec2 in peripheral mononuclear cells (MNCs) and polymorphonuclear neutrophils (PMNs) as a model of humoral circadian transmission in healthy young male volunteers. We obtained blood samples every 2 hours under modified constant routine conditions, and extracted mRNA for real-time quantitative PCR analysi using TaqMan fluorogenic probes and corresponding primer sets. We detected significant expression all of the 10 circadian clock genes in both the MNCs and PMNs. Gene expression of hPer1, hPer2, hPer3, Cry1, Cry2, Dec1, Dec2 in MNCs and PMNs showed significant daily variations, while Clock showed no significant circadia
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n variation as described in the suprachiasmatic nucleus (SCN), the circadian master clock, and peripheral tissues in nocturnal animals. Additionally, hPer1, hPer2, hPer3 showed similar acrophases and peak transcription in the transition period from subjective night to subjective day (early subjective morning). Especially, the acrophases in hPer1 expression rhythms in MNCs and PMNs were found to correlate positively with that of the serum melatonin secretion rhythms, which is a reliable phase marker of the SCN. The present findings indicate that clock gene activity could be preserved across different peripheral blood cell types and support the assumption that peripheral clocks are entrained by the SCN. There were no significant differences in hPer1, hPer2, hPer3 expression in MNCs between healthy young and 60s elderly subjects. This suggests that ability of entrainment of peripheral clocks to the circadian humoral signals oscillating from the SCN is maintained at least in the healthy elderly subjects until 60s under entrained condition. Conversely, we observed internal desynchronization among body temperature, melatonin, cortisol and hPer gene family expression rhythms showing different free-running periods in non-24 sleep-wake rhythm patients. These findings suggest diversity of mode of circadian humoral/neuronal signal transmission in humans. Less
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