SLEEP 2011 Abstract Supplement

A. Basic Science V. Physiology
Conclusion: A profound ACR was observed in this sample of children
with effect sizes similar to that found in adults. After only one night of
sleep restriction, evidence of a blunted ACR was apparent. These data
warrant further investigation into the cognitive, emotional, and behavioral
correlates of a blunted ACR. Striking ACRs following morning and
afternoon naps and a flattened ACR after an evening nap indicate short
sleep periods are sufficient to produce ACRs when the timing of wake
does not coincide with the circadian cortisol nadir.
Support (If Any): K01MH74643 to LeBourgeois
0113
SLOW WAVE SLEEP, BUT NOT INSOMNIA, IS ASSOCIATED
WITH DIMINISHED ANTIBODY RESPONSE TO A HEPATITIS
B VACCINE
Pigeon WR 1,2 , Perlis ML 3 , Erdman E 4 , Gorman C 1 , Casey C 1 ,
Heffner K 2 , Moynihan J 2
1
Sleep & Neurophysiology Research Laboratory, University of
Rochester, Rochester, NY, USA, 2 Psychiatry, University of Rochester,
Rochester, NY, USA, 3 Psychiatry, University of Pennsylvania,
Philadelphia, PA, USA, 4 Psychiatry, Yale University, New Haven, CT,
USA
Introduction: Despite its prevalence and associated morbidities, the
pathophysiology by which insomnia confers morbidity risk is relatively
unstudied. With respect to medical morbidity, diminished immunocompetence
is one possible pathway. The current study was conducted to
investigate whether 1) insomnia, compared to good sleep, or 2) any specific
objective sleep measure was associated with a diminished immune
response to a vaccine challenge.
Methods: The study enrolled 28 pre-menopausal female subjects aged
25-50 with either Psychophysiologic Insomnia (PI) or Good Sleep (GS)
into a parallel two-group design; 19 subjects (8 PI and 11 GS) completed
the study. Following two consecutive nights of polysomnography
(PSG), subjects received a 3-part Hepatitis B (Hep B) vaccine regimen
at 0, 1, and 2 months post-PSG. Blood was obtained at 0, 1, 2, and 3
months, centrifuged and stored at -80°C. Serum samples were subsequently
tested by radioimmunoassay to detect titer levels of antibodies
to Hepatitis B surface antigen. Protective titer levels (seroconversion)
are defined as >10 mIU/mL.
Results: Seroconversion rates did not differ by group. The groups did
differ, in the opposite direction than expected, on antibody titer levels.
Namely, the PI group had significantly higher titer levels than the GS
group across the three time points (p< .05 in a mixed model). Among
PSG measures, Slow Wave Sleep (SWS) minutes were higher in subjects
who seroconverted compared to those not achieving protective levels
(p=.03). No other PSG measure differentiated sero-conversion status.
Amount of SWS was also positively correlated with titer levels (r=.724;
p=.002 for titer 2 and r=.556; p=.025 for titer 3). Notably, neither age nor
depression severity (which was minimal in most cases) was related to
seroconversion rates or to titer levels, making the findings with respect
to SWS intriguing.
Conclusion: These findings suggest that SWS may serve a protective
function with respect to immunogenicity. This is consonant with findings
from a nascent literature suggesting that diminished SWS is associated
with elevated levels of proinflammatory cytokines, another marker of
immune function. In addition, since decrements in the SWS of subjects
with insomnia compared to good sleepers have been observed in some
investigations, but not others, this may 1) further explain why insomnia
status may not be as good a predictor of immune response as amount of
SWS, and 2) underscore the importance of SWS as a therapeutic target.
Support (If Any): This work was supported by NIH K23NR010408,
the Rochester Center for MindBody Research (R21AG023956) and the
University of Rochester Clinical and Translational Science Institute.
0114
SLEEP DEPRIVATION AND INFLAMMATION IN A MURINE
MODEL
Shea TJ 3 , Buzzetti R 1 , Ibuki Y 1 , Sirakis GD 1,2 , Hinojosa-Kurtzberg M 1,2 ,
Parthasarathy S 1,2
1
Research Service Line, Southern Arizona VA HealthCare System,
Tucson, AZ, USA, 2 Arizona Respiratory Center, University of Arizona,
Tucson, AZ, USA, 3 University of Arizona, Tucson, AZ, USA
Introduction: In rodent experimental models of sleep deprivation,
shortening sleep duration has resulted in elevation of pro-inflammatory
cytokines, but has involved increased physical activity which may have
been responsible for the pro-inflammatory effects. A recently validated
method of sleep deprivation can produce gentle movement of mice by a
timed orbital shaker without increased physical activity and would allow
the study of the relationship between sleep deprivation and inflammation
without the confounding influence of physical activity. We set out to
study the effects of chronic sleep deprivation (21 days) on inflammation
in a murine model of sleep deprivation without the confounding influence
of increments in physical activity.
Methods: Thirty-three mice (C57Bl/6; JAX, Bar Harbor, ME) were
subjected to either chronic sleep deprivation (n=16) or control condition
(n=17), but blood obtained through cardiac puncture was available in
only 22 animals (11 controls, and 11 sleep deprived). Sleep deprivation
was achieved by placing the mice in cages on orbital shakers that were
gently activated by timers during the light cycle for 19 days and followed
by activation over 24 hours/day for 2 days.
Results: Interleukin-6 level was greater in the sleep deprived group
(median of 15.6; IQR, 9.2, 22.8) than in control group (4.7, IQR, 4.7,
6.9; P=0.038). Similarly, IL-2 level was greater in the sleep deprived
group (median 52; IR, 32, 272) than in control group (16.1; IQR, 12.1,
16.1; P=0.049). Also, IL-4 levels were greater in the sleep deprived
group (median of 133.8; IQR, 113, 228) than in control group (100.0,
IQR, 88.6, 100.0; P=0.046). Whereas, IL-17a level tended to be greater
in the sleep deprived group (median of 0.02; IQR, 0.01, 0.1) than in control
group (0.007, IQR, 0.005, 0.008; P=0.05). But, Macrophage colony
stimulating factor was lower in the sleep deprived group (median of 3.0;
IQR, 2.4, 3.9) than in control group (5.0, IQR, 3.8, 15.8; P=0.033). Also,
Growth regulated alpha-protein level was lower in the sleep deprived
group (median 0.07; IQR, 0.02, 0.09) than in control group (median
0.16; IQR, 0.07, 0.28; P=0.014). Moreover, IL-1β, IL-7, IL-10, and IL-
11 levels were not different between the two groups.
Conclusion: In this exploratory study, chronic sleep deprivation -- without
the confounding influence of increments in physical activity -- was
associated with a pro-inflammatory state.
Support (If Any): Johrei Foundation
0115
EFFECTS OF NEUROMODULATORY SUBSTANCES ON THE
ACTIVITY OF SLEEP-ACTIVE CORTICAL NEURONS
Heiss J, Dittrich L, Kilduff TS
Biosciences, SRI International, Menlo Park, CA, USA
Introduction: Recently, we described a sleep-active neuronal population
in the cerebral cortex. These cells express NPY, nNOS and the NK1
receptor. Substance P (SP) promoted wakefulness when injected ICV
in rats (Andersen et al. 2006) or IV in humans (Lieb at al. 2002), while
microinjections in the ventrolateral preoptic area promoted sleep (Zhang
et al. 2004). To test the hypothesis that SP can modulate the activity of
cortical sleep-active neurons, we performed in vitro patch clamp recordings
of putative sleep active neurons while delivering SP as well as other
compounds to the bath.
Methods: Patch clamp recordings were performed in cortical slices of
transgenic Npy-hrGFP mice. Putative sleep-active neurons were identified
as large green fluorescent neurons located in cortical layers 5 and
6. The effect of SP (150 nM), ACh (0.1 mM), 5-HT (0.5 mM) and other
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SLEEP, Volume 34, Abstract Supplement, 2011