SLEEP 2011 Abstract Supplement

A. Basic Science XI. Sleep Deprivation
0263
CHRONIC SLEEP FRAGMENTATION INCREASES
MITOCHONDRIAL REACTIVE OXYGEN SPECIES
PRODUCTION AND OXIDATIVE STRESS IN CORTEX
Kaushal N, Ramesh V, Zhang S, Wang Y, Gozal D
Pediatrics, University of Chicago, Chicago, IL, USA
Introduction: Sleep fragmentation (SF) is an important component of
many sleep disorders, including obstructive sleep apnea and is believed
to contribute to end-organ morbidity. However, the mechanisms underlying
SF-associated functional alterations remain elusive.
Methods: C57BL/6 mice (n=7) were chronically implanted with telemetric
transponders to measure EEG, EMG, body temperature (Tb) and
gross activity (Ag) at 8 months. After surgical recovery, the mice were
acclimatized in a custom developed SF chamber. Following that, the
mice were subjected to 15 days of chronic SF for 12 hours/day from
7am to 7pm (every 2 min). Sleeping mice served as control. After the
SF procedure the mice were sacrificed, and the brain was harvested
and dissected. The cortex was assayed for the oxidative markers malondialdehyde
(MDA) and 8-hydroxy-2’-deoxyguanosine (8-OHdG). In
addition, mitochondrial isolation was conducted in cortices from SF
and control and ROS production was determined using flow cytometric
approaches.
Results: Following 15 days of SF, there were significant increases in
both MDA and 8-OHdG in the cortex. In live isolated mitochondria, a
marked increase in ROS production was apparent.
Conclusion: SF induces oxidative stress in cortex via mechanisms that
involve excessive production of ROS in mitochondria.
Support (If Any): NIH grant HL 086662 (DG)
0264
SLEEP DEPRIVATION UNDER SUSTAINED HYPOXIA
PROTECTS AGAINST OXIDATIVE STRESS
Ramanathan L 1,2 , Siegel J 1,2
1
Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA,
USA, 2 Neurobiology Research, VAGLAHS, North Hills, CA, USA
Introduction: We previously showed that sleep deprivation alters antioxidant
responses in several rat brain regions. We also reported that
chronic hypoxia modifies antioxidant responses and increases oxidative
stress in rat cerebellum and pons, relative to normoxic conditions. In the
current study, we exposed rats to (6h) sleep deprivation under sustained
hypoxia (SDSH), and compared changes in antioxidant responses and
oxidative stress, in the neocortex, hippocampus, brainstem and cerebellum,
to those occurring in control animals subjected to the same level of
sustained hypoxia but left undisturbed (UCSH).
Methods: We measured changes in total nitrite levels, as an indicator
of nitric oxide production, superoxide dismutase (SOD) activity and total
glutathione (GSHt) levels as markers of antioxidant responses, and
levels of thiobarbituric acid reactive substances (TBARS) and protein
carbonyls, as signs of lipid and protein oxidation products, respectively.
We also measured changes in the activity of hexokinase (HK), the rate
limiting enzyme in glucose metabolism.
Results: We found that SDSH increased nitric oxide levels and decreased
the levels of TBARS in the rat hippocampus relative to control
hypoxic conditions. On the other hand, SDSH decreased nitric oxide
levels and increased GSHt levels in the rat cerebellum relative to UCSH.
Furthermore, SDSH increased GSHt levels, without affecting the levels
of either nitric oxide, TBARS or carbonyl proteins in the rat neocortex
and brainstem, compared to UCSH. SOD activity was not affected in
any of the brain regions studied here. Additionally, we observed an increase
in HK activity in the neocortex of SDSH rats compared to UCSH
rats, suggesting that elevated glucose metabolism may be a potential
source of increased free radical production in this brain region.
Conclusion: We conclude that acute (6h) SDSH differentially affects
various rat brain regions, but overall it protects against oxidative stress.
Short term insomnia may therefore serve as an adaptive response to prevent
sustained hypoxia-induced cellular injury.
Support (If Any): Research supported by NS14610, MH64109 and the
Medical Research Service of the Department of Veterans Affairs.
0265
SLEEPLESS NIGHTS AND STRESSFUL DAYS: SLEEP
DEPRIVATION AND MENTAL STRESS AMPLIFY SURGES IN
BLOOD PRESSURE
Franzen PL 1 , Gianaros PJ 1 , Marsland AL 2 , Hall MH 1,2 , Siegle GJ 1 ,
Dahl R 3 , Buysse DJ 1
1
Department of Psychiatry, University of Pittsburgh School of
Medicine, Pittsburgh, PA, USA, 2 Department of Psychology,
University of Pittsburgh, Pittsburgh, PA, USA, 3 Department of Public
Health, University of California Berkeley, Berkeley, CA, USA
Introduction: Sleep disturbances and psychological stress are highly
prevalent, and both are implicated in the etiology of cardiovascular diseases.
Given their tendency to co-occur, they may act synergistically in
cardiovascular pathogenesis. To test for additive effects of sleep deprivation
and psychological stress on blood pressure, we examined acute
stress reactivity following rested and sleep-deprived experimental conditions
in healthy young adults.
Methods: Participants included 20 young adults 20-25 years old free
from current or past sleep, psychiatric, or major medical disorders. Using
a within-subjects crossover design, we examined acute stress reactivity
under two experimental conditions: following a night of normal
sleep in the laboratory and following a night of total sleep deprivation.
Two standardized psychological stress tasks were administered, a Stroop
color-word naming interference task and a speech task, which were preceded
by a pre-stress baseline and followed by a post-stress recovery
period. Each period was 10 minutes in duration, and blood pressure
recordings were collected every 2.5 minutes throughout each period.
Mean blood pressure responses during the stress and recovery periods
were examined with a mixed effects analysis of covariance, controlling
for baseline blood pressure.
Results: There was a significant interaction between sleep deprivation
and stress on systolic blood pressure, F(2,83.4)=4.35, p=0.016. Systolic
blood pressure was higher in the sleep deprivation condition compared
with the normal sleep condition during the speech task, t(18)=2.93,
p=0.009), whereas blood pressure did not differ between the sleep conditions
during the Stroop task or the post-stress recovery period.
Conclusion: Sleep deprivation amplified systolic blood pressure increases
to psychological stress. Sleep loss may increase cardiovascular
risk by dysregulating stress physiology. Based on these data, stress may
be particularly important to address in individuals with sleep problems
and vice versa in reducing cardiac vulnerability. Educational or behavioral
interventions to prevent sleep loss could buffer the adverse health
outcomes associated with stress.
Support (If Any): K01 MH077106 UL1 RR024153 National Sleep
Foundation Pittsburgh Mind-Body Center Health Research Formula
Funds from the Pennsylvania Department of Health (Act 2001-77)
0266
INCREASES IN NOREPINEPHRINE ARE ASSOCIATED
WITH FEWER MICROSLEEPS DURING SUSTAINED
WAKEFULNESS
Simpson N, Cahalan C, Haack M, Mullington JM
Neurology, Beth Israel Deaconess Medical Center/Harvard Medical
School, Boston, MA, USA
Introduction: Sleep loss is a significant and unique stressor, as sleep
itself is a biological resource necessary to regulate multiple physiological
systems. It was hypothesized that levels of norepinephrine, a marker
of autonomic activation, would increase in response to sleep loss while
levels of self-reported stress would not.
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SLEEP, Volume 34, Abstract Supplement, 2011