SLEEP 2011 Abstract Supplement

A. Basic Science VI. Chronobiology
0182
EVALUATION OF INDIVIDUAL’S CIRCADIAN CLOCK
PROPERTIES AT PHYSIOLOGICAL AND MOLECULAR
LEVELS
Hida A, Kitamura S, Watanabe M, Enomoto M, Aritake S, Higuchi S,
Nozaki K, Kato M, Moriguchi Y, Mishima K
Department of Psychophysiology, National Center of Neurology and
Psychiatry, Tokyo, Japan
Introduction: Behavioral and physiological processes such as sleepwakefulness,
thermoregulation and hormone secretion exhibit circadian
rhythms in most organisms including humans. These rhythms are driven
by a system of self-sustained clocks and are entrained by external cues
such as cycles of light and dark and food intake. The mammalian central
oscillator, the suprachiasmatic nuclei (SCN) incorporates environmental
information and orchestrates slave oscillators in peripheral cells. The
circadian clock system is composed of a hierarchy of oscillators that
involve transcription and translation feedback loops of multiple clock
genes. Disorganization of the circadian system is known to be closely
related to many diseases including sleep, mood and metabolic disorders.
Advanced sleep phase type, delayed sleep phase type and non-entrained
type of circadian rhythm sleep disorders (CRSD) are thought to result
from malfunction/maladaptation of the circadian system. Dissection of
human circadian clock system is indispensable to understand the pathophysiology
of CRSD. However, it is difficult and expensive to assess
individual’s circadian rhythms precisely. Therefore, more convenient
measurements of circadian properties are demanded to reduce patients’
burden, since they are usually required to stay in a laboratory environment
free from external cues and masking effects for over a couple of
weeks.
Methods: In this study, we evaluated rhythmic characteristics of physiological
functions (core body temperature, plasma melatonin and plasma
cortisol levels) from 14 healthy male subjects under a 28-h forced desynchrony
protocol. Furthermore, we assessed clock gene expression in
primary fibroblast cells established from individual’s skin biopsies using
a luminescence reporter assay system.
Results: We compared the period of bioluminescence rhythms with
the period of physiological rhythms in the same subjects and found that
there was a highly significant correlation between the period length of
fibroblast rhythms and physiological rhythms.
Conclusion: Our results suggest that surrogate measurements using fibroblast
cells would be a powerful tool for assessing individual’s circadian
properties.
0183
AN ENDOGENOUS CIRCADIAN RHYTHM IN BAROREFLEX
SENSITIVITY THAT PEAKS DURING THE BIOLOGICAL
NIGHT
Hu K, Scheer FA, Garcia JI, Laker M, Marks J, Hussain MV, Shea SA
Division of Sleep Medicine, Brigham and Women’s Hospital, Harvard
Medical School, Boston, MA, USA
Introduction: Blood pressure (BP) is regulated acutely by negative
feedback involving arterial baroreceptors that provoke autonomic nervous
system changes resulting in altered heart rate, cardiac contractility,
and vasoconstriction to maintain BP. The change in heart beat interval
per change in BP is used as an index of baroreceptor sensitivity (BRS).
We tested whether BRS exhibits an endogenous circadian pattern. If
BRS is lower during the biological night, this could explain the endogenous
circadian rhythm in vulnerability to presyncope that peaks during
circadian phases corresponding to the biological night (Hu et al. 2008
Sleep 31, Suppl. A25).
Methods: Twelve healthy subjects (6 females, 20-42 years old) underwent
a 13-day in-laboratory protocol, in which each subject’s “day”
length was adjusted to 20 hours so that behaviors distribute evenly
across the circadian cycle. A 15-minute title-table test (60° head-up) was
performed ~4.5 hours after scheduled awakening in each 20-hour cycle.
ECG and beat-to-beat BP were recorded to estimate BRS. Core body
temperature was used as a circadian phase marker.
Results: From a mean baseline BRS of 15.4±1.7 (SE) ms/mmHg, BRS
declined by 57.2±4.7% within one minute of tilting up (p