Daily rhythms generated by endogenous circadian mechanisms and synchronized to the light-dark cycle have been implicated in the timing of birth in a wide variety of species. Although chronodisruption (e.g., shift work or clock gene mutations) is associated with poor reproductive outcomes, little is known about circadian timing during pregnancy. This study tested whether daily rhythms change during full-term pregnancies in mice and women. We compared running wheel activity continuously in both nonpregnant ( n = 14) and pregnant ( n = 13) 12- to 24-week-old C57BL/6NJ mice. We also monitored wrist actigraphy in women ( N = 39) for 2 weeks before conception and then throughout pregnancy and measured daily times of sleep onset. We found that on the third day of pregnancy, mice shift their activity to an earlier time compared with nonpregnant dams. Their time of daily activity onset was maximally advanced by almost 4 h around day 7 of pregnancy and then shifted back to the nonpregnant state approximately 1 week before delivery. Mice also showed reduced levels of locomotor activity during their last week of pregnancy. Similarly, in women, the timing of sleep onset was earlier during the first and second trimesters (gestational weeks 4-13 and 14-27) than before pregnancy and returned to the prepregnant state during the third trimester (weeks 28 until delivery). Women also showed reduced levels of locomotor activity throughout pregnancy. These results indicate that pregnancy induces changes in daily rhythms, altering both time of onset and amount of activity. These changes are conserved between mice and women.

Cognition is modulated by circadian rhythms, in both nocturnal and diurnal species. Rhythms of clock gene expression occur in brain regions that are outside the master circadian oscillator of the suprachiasmatic nucleus and that control cognitive functions, perhaps by regulating the expression neural-plasticity genes such as brain derived neurotrophic factor (BDNF) and its high affinity receptor, tyrosine kinase B (TrkB). In the diurnal grass rat (Arvicanthis niloticus), the hippocampus shows rhythms of clock genes that are 180° out of phase with those of nocturnal rodents. Here, we examined the hypothesis that this reversal extends to the optimal phase for learning a hippocampal-dependent task and to the phase of hippocampal rhythms in BDNF/TrkB expression. We used the Morris water maze (MWM) to test for time of day differences in reference memory and monitored daily patterns of hippocampal BDNF/TrkB expression in grass rats. Grass rats showed superior long-term retention of the MWM, when the training and testing occurred during the day as compared to the night, at a time when nocturnal laboratory rats show superior retention; acquisition of the MWM was not affected by time of day. BDNF/TrkB expression was rhythmic in the hippocampus of grass rats, and the phase of the rhythms was reversed compared to that of nocturnal rodents. Our findings provide correlational evidence for the claim that the circadian regulation of cognition may involve rhythms of BDNF/TrkB expression in the hippocampus and that their phase may contribute to species differences in the optimal phase for learning.

The same clock-genes, including Period (PER) 1 and 2, that show rhythmic expression in the suprachiasmatic nucleus (SCN) are also rhythmically expressed in other brain regions that serve as extra-SCN oscillators. Outside the hypothalamus, the phase of these extra-SCN oscillators appears to be reversed when diurnal and nocturnal mammals are compared. Based on mRNA data, PER1 protein is expected to peak in the late night in the paraventricular nucleus of the hypothalamus (PVN) of nocturnal laboratory rats, but comparable data are not available for a diurnal species. Here we use the diurnal grass rat (Arvicanthis niloticus) to describe rhythms of PER1 and 2 protein in the PVN of animals that either show the species-typical day-active profile, or that adopt a night-active profile when given access to running wheels. For day-active animals housed with or without wheels, significant rhythms of PER1 or PER2 protein expression featured peaks in the late morning; night-active animals showed patterns similar to those expected from nocturnal laboratory rats. Since the PVN is part of the circuit that controls pineal rhythms, we also measured circulating levels of melatonin during the day and night in day-active animals with and without wheels and in night-active wheel runners. All three groups showed elevated levels of melatonin at night, with higher levels during both the day and night being associated with the levels of activity displayed by each group. The differential phase of rhythms in clock-gene protein in the PVN of diurnal and nocturnal animals presents a possible mechanism for explaining species differences in the phase of autonomic rhythms controlled, in part, by the PVN. The present study suggests that the phase of the oscillator of the PVN does not determine that of the melatonin rhythm in diurnal and nocturnal species or in diurnal and nocturnal chronotypes within a species.

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