The early life condition: Importance for sleep, circadian rhythmicity, behaviour and response to later life challenges
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Early life environment has a vast impact on development and adult functioning. Optimal brain development depends not only on genetic programming but also on specific external stimuli, where mother-infant relationships play an important role. In rats, through maternal presence and active care, important stimuli are provided which influence the development of behaviour and basic physiological functions in the offspring such as sleep, circadian rhythms and stress-regulating mechanisms. Events in early life can define the development of the offspring, and depending on the events’ timing and duration, may induce long-term positive or negative consequences. If the events are adverse they may induce enhanced vulnerability to stress exposure later in life. Clinical studies have revealed a close link between adverse early life events and development of affective disorders in adulthood. Underlying mechanisms are commonly studied using experimental models of early life adverse events based on daily separations of infant rats from their mothers for periods longer than considered natural, in comparison to other more natural early life conditions. The main aim of this study was to investigate three early life conditions in rats, long maternal separations (LMS), brief maternal separations (BMS) or non-handling (NH), and their consequences in adulthood on: brain activity, sleep, circadian rhythms, levels of corticosterone, affective-like behaviour and cognitive performance. Effects of early life conditions in combination with exposure to chronic mild stress (CMS) in adulthood were also investigated. Such a combination, which yields a potentially high etiological and construct validity, has not received great attention in the preclinical literature. Paper I investigated the consequences on brain activity measured by electroencephalogram (EEG) power and sleep in adult LMS and BMS offspring. As an effect of early life condition, adult LMS offspring showed lower EEG power recorded from the frontal cortical structures during both sleep and wakefulness, compared to BMS offspring. The quality of slow wave sleep (SWS) differed as a consequence of maternal separation. LMS offspring showed more deep SWS but lower power of delta waves and a slower reduction of the sleep pressure compared to BMS offspring. Exposure to CMS led to similar reductions in EEG power during sleep and wakefulness and affected reduction of sleep pressure in both groups. Compared to BMS offspring, the lower EEG power was still present in LMS offspring who also showed longer total sleep time and an indication of higher pressure for rapid eye movement (REM) sleep. In Paper II, the consequences on circadian rhythmicity of body temperature, locomotor activity and heart rate were investigated in adult LMS and BMS offspring. As an effect of early life condition, LMS offspring showed a delayed circadian peak of body temperature compared to BMS offspring. Investigation of all other parameters showed that circadian rhythms of body temperature, locomotor activity and heart rate were similar between adult LMS and BMS offspring. The stronger impact of CMS exposure in LMS offspring was evident in stronger and longer lasting reduction of body temperature compared to BMS offspring. The degree of mothers’ active care was reflected in the degree of hypothermia in LMS offspring. More active nursing following maternal separation moderated the severity of hypothermia. In Paper III, consequences of three early life conditions, LMS, BMS and NH were investigated measuring levels of corticosterone, affective-like behaviour and cognitive performance. LMS offspring displayed higher basal level of corticosterone than BMS offspring and both NH and LMS offspring showed poor cognitive performance measured by lower object exploration compared to BMS offspring. NH also showed lower pre-pulse inhibition than LMS and BMS offspring. These results reflect adverse consequences of both LMS and the condition with constant presence of the mother. There were no differences in affective-like behaviour between the three early life conditions. Exposure to CMS induced an anhedonic-like state in all offspring. An initially high level of corticosterone was not further elevated by CMS in LMS offspring, whereas they explored objects less compared to BMS offspring. Upon CMS exposure, both BMS and NH offspring increased their object exploration. A positive effect of CMS in NH offspring was also indicated by increased habituation and pre-pulse inhibition in acoustic startle test. The present study describes consequences of different early life conditions (LMS, BMS or NH) on adulthood functioning and different consequences of exposure to chronic stressors in adulthood. Overall, the results indicate that exposure to LMS during early life may have adverse consequences for brain functioning as reflected in measures of brain activity and cognitive performance. Results in BMS offspring confirm that brief separations early in life may provide a “toughening up” effect in adulthood. Exposure to CMS affected brain activity in both LMS and BMS offspring. More severe impact was observed on cognitive performance and thermoregulatory response in the LMS offspring; importantly, active maternal care reduced the negative consequence of CMS. Brain activity was not assessed in the NH offspring, while the results on cognitive performance suggest adverse consequences of early life condition with the constant presence of the mother. However, remarkably, the results indicate that adult exposure to chronic mild stressors mimicking daily hassles in humans may produce a positive effect in NH offspring. Overall, the present findings reveal that different experiences and hence different developmental conditions during early life may have consequences for adulthood brain functioning.
Består avPaper I: Mrdalj J., Pallesen S., Milde A.M., Jellestad F.K., Murison R., Ursin R., Bjorvatn B. and Grønli J. (2013). Early and later life stress alter brain activity and sleep in rats. PLoS ONE 8 (7): e69923. The article is available here: http://hdl.handle.net/1956/9544
Paper II: Mrdalj J., Mattson, Å.L., Murison R., Jellestad F.K., Milde A.M., Pallesen S., Ursin R., Bjorvatn B. and Grønli J. (2014). Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations. Chronobiology International 31(2): 252–264. Full-text not available in BORA. The published version of the article is available here: http://dx.doi.org/10.3109/07420528.2013.846351
Paper III: Mrdalj J., Murison R., Soulé J., Kinn Rød A.M., Milde A.M., Pallesen S. and Grønli J. Toughening up effect of adult chronic mild stress in rats experiencing brief maternal separations or the constant presence of the mother early in life. Submitted manuscript. Full-text not available in BORA.