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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.
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