BARBARA TATE



Longitudinal Studies Of The Circadian Rhythm Of A Juvinile Diurnal Mammal

BARBARA TATE, Ph.D.
GARY S. RICHARDSON, M.D.
Division of Geriatric Medicine
The Miriam Hospital

mong the most prominent changes in sleep patterns associated with human adolescence is a delay in the timing of sleep. In addition to psycho-social factors, biological processes may contribute to altered sleep patterns. The central role of the circadian clock in sleep-wake orgaization suggests that peripubertal alterations in the circadian system may underlie changes in the timing of sleep during adolescence. Animal models are useful for examination of mechanisms responsible for changes in circadian organization, particularly distinguishing between chronological and maturational processes, as these studies require manipulation of sex steroid levels by gonadectomy or steroid administration. The goal of the studies described here is to investigate whether characteristics of circadian rhythms are altered during the period of sexual maturation. A unique animal model, the Octodon degu, is employed in these studies.

The degu is an hystricomorph rodent native to Chile and Peru with a number of features that make it suitable for developmental studies of sleep and circadian rhythms. The most appealing feature of the degu is its diurnal pattern of behavior. Unlike the nocturnal rat, mouse and hamster, the degu shows a circadian rise in body temperature in the morning and a peak in activity in the late morning/early afternoon. The phase relationship between the light/dark cycle and the sleep/wake rhythm is analogous to that of primates and unlike that of most rodents. In addition, although precocial, degus displays a delayed onset of puberty, with neither sex obtaining reproductive competence until approximately 4 months of age. Thus, the juvenile period is of duration sufficient to allow assessment of developmental alterations in circadian rhythms associated with sexual maturation. In the studies described here, we examined the phase and circadian pattern of the activity rhythm during the developmental period from weaning through young adulthood.

Litters of degus were born on light/dark cycles of 12 hours of light and 12 hours of dark (LD 12:12, lights on at 0700). Male and females were weaned at 4 weeks of age and housed in individual cages. Each cage was equipped with a stainless steel running wheel. In the first study, animals remained in LD 12:12 lighting schedules and running wheel activity was continuously recorded until 25 weeks of age. Activity onset times were calculated for weeks 4 though 25. Body weight, testes size and vaginal opening were also determined periodically. Serum and anterior pituitaries were collected from siblings of subjects at intervals thought the data collection period. In a second study designed to examine longitudinal changes in free running period (tau), weaned pups were implanted with a radio transmitter and transferred to constant dim red light. Activity and body temperature data were continuously collected. Each animal also had access to a running wheel as in Study 1. Tau was assessed with Enright chi-squared periodogram at 10 day intervals throughout the data collection period.

Result of the first study show that body mass exhibited the sharpest increase between ages 4 and 8 weeks, with maximum body weight reached at 16 weeks of age. Maximum testes size and vaginal openings were also reached by 16 weeks of age. The phase of running wheel activity onsets in the entrained population ranged from 3.33 hours prior to lights on to 0.86 after lights on. Activity onset times appear to be consistent within a litter, indicating a possible genetic component to the timing of phase of activity onset. Across development, the population showed a trend for later activity onset with advanced age. Preliminary analysis of data from animals exposed to constant dim red light also suggests a lengthening of tau as the animals progress through development. Taken together these data suggest a developmental phase delay in wake onset reflecting a progressive lengthening in tau. The relationship of these changes to specific aspects of sexual maturation remains to be determined. In addition, these results support the use of the Octodon degu as an experimental model with which to study developmental changes in sleep wake-timing.