母子分離によるリズム同調とストレス脆弱性

抄録

The life of newborn rats totally depends on their maternal care. Although the first several days of their life are characterized by stress-hyporesponsiveness, absence of mother acts as a strong stressor which overrides it and results in long-lasting stress-vulnerability. Periodic maternal deprivation (MD) for the first few days act as a strong non-photic time cue and entrains pups' circadian clock. However, little is known as to the mechanisms how the MD affects on the pups' circadian clock and stress-responsiveness in the adulthood. We imposed newborn rats to MD of various durations at different time in the light phase, at different period in the postnatal life, with or without keeping pups warm. In addition, by restricting food access of mother rats to 2h (RF), behavioral rhythms of mothers were modified without depriving them from pups. We measured clock gene expression rhythms in the suprachiasmatic nucleus of the fetes and neonates, and behavioral rhythms after weaning. At 8 weeks of age, stress responsiveness was examined by measuring plasma corticosterone levels after exposing to mild stress of cage exchange. 12 h MD during the light phase in day1-6 completely reversed the circadian rhythms of clock gene expression. The behavioral rhythms after weaning were also shifted depending on the phase of MD. Rats exposed to MD exhibited hyper responsiveness to the novelty stimuli, which was abolished by MD with warming. These results suggest that the maternal care is important to entrain pups' clock, while heat loss due to isolation is critical for the stress hyper-responsiveness in adulthood. [J Physiol Sci. 2006;56 Suppl:S25]