SLEEP 2011 Abstract Supplement

A. Basic Science III. Ontogeny/Aging
0058
INTERMITTENT HYPOXIA-INDUCED WHITE MATTER
LESIONS IN NEONATAL MICE
Cai J 1 , Tuong C 2 , Zhang Y 3 , Shields CB 4 , Gozal D 5
1
Pediatrics/KCH Res. Inst., Anatomical Sciences and Neurobiology,
University of Louisville School of Medicine, Louisville, KY, USA,
2
Pediatrics/KCH Res. Inst., University of Louisville School of
Medicine, Louisville, KY, USA, 3 Norton Neuroscience Institute,
Norton Healthcare, Louisville, KY, USA, 4 Norton Neuroscience
Institute, Norton Healthcare, Louisville, KY, USA, 5 Pediatrics,
University of Chicago, Chicago, IL, USA
Introduction: Recent studies from both clinical and animal research
suggest that diffuse structural changes in brain white Recent studies
from both clinical and animal research suggest that diffuse structural
changes in brain white matter are a positive predictor of poor cognitive
outcomes. We hypothesize that infantile apnea could lead to and/or exaggerate
white matter impairment. To test this hypothesis, oligodendroglia
and axon development were investigated in neonatal mouse model of
intermittent hypoxia (IH) between postnatal days 2 to 10.
Methods: P2 C57BL/6 pups were exposed to either 4 to 8 days of intermittent
hypoxia (IH, 8% or 5.7% O2 / 20.9% O2 /120s or 140s each
cycle/6hrs) or intermittent air (IA) with pseudo dam during the light
phase. After IA or IH exposure, all pups were restituted to their lactating
dam in room air. The brains were collected at 4 and 8 post-exposure
days. Oligodendrocyte-specific proteins, neurocytoskeletal and synapserelevant
molecules, ultra-structure of myelinated axons, and electrophysiological
function were examined at different post-exposure days in
IA- and IH-treated developing mice.
Results: Short-term neonatal IH exposure induced hypomyelination in
brain regions, including corpus callosum, striatum, fornix and cerebellum,
but not pons or spinal cord. Myelin-forming process was disturbed
by lack of myelin proteins due to arresting the maturation of oligodendrocytes.
Immature oligodendrocytes were more vulnerable to neonatal
IH exposure than developing axons. Insufficient neurofilament (NF)
synthesis with anomalous components of NF subunits, β-tubulin and
MAP2 isoforms indicated immaturity of axons in IH-exposed mouse
brains. In addition, down-regulation of Synapsin I, Synaptophysin and
Gap-43 phosphorylation suggested a potential stunt in axonogensis and
synaptogenesis. This region-selective and complex white matter impairment
was further associated with electromicroscopic abnormalities and
electrophysiological changes.
Conclusion: These findings suggest that IH insult during sleep in neonates,
as occurs in apnea of prematurity, may couple disturbance of
myelinogenesis and axonal immaturation within a critical window of
CNS development, which could in turn cause long-term neurobehavioral
sequelae.
Support (If Any): NIH 2P20RR017702-061A1 (R.M.G., J.C. is CO-
BRE supported junior faculty and co-investigator), Sleep Research Society
Foundation/J. Christian Gillin M.D. Research Grant (J.C.), University
of Louisville SOM Basic Grant (J.C.), and NIH HL-086662 (D.G.).
0059
LONGITUDINAL ASSOCIATION BETWEEN SHORT
SLEEP AND BODY WEIGHT, ANXIOUS/DEPRESSED, AND
LEARNING IN HISPANIC AND CAUCASIAN CHILDREN
Silva GE 1 , Goodwin JL 2 , Parthasarathy S 2 , Sherrill DL 3 , Vana KD 1 ,
Drescher AA 3 , Quan SF 4
1
College of Nursing and Healthcare Innovation, Arizona State
University, Phoenix, AZ, USA, 2 College of Medicine, University of
Arizona, Tucson, AZ, USA, 3 College of Public Health, University of
Arizona, Tucson, AZ, USA, 4 Division of Sleep Medicine, Harvard
Medical School, Boston, MA, USA
Introduction: Cross-sectional studies have reported associations between
shorter sleep and high body mass index (BMI). However, few
longitudinal studies have assessed this relationship from childhood to
young adulthood, and none has assessed sleep using polysomnography
(PSG). This study aimed to determine the impact of lower amounts of
childhood sleep determined by PSG on development of obesity, being
anxious or depressed, or having learning problems five years after.
Methods: A prospective cohort included 304 community participants
from the Tucson Children’s Assessment of Sleep Apnea study, aged
6-10 years old at baseline. Children were classified according to baseline
sleep as normal sleepers (slept ≥ 9 hours/day), short sleepers (slept > 7.5
- < 9 hours/day), and very short sleepers (slept ≤ 7.5 hours/day). Odds
of overweight/obese (≥85th BMI percentile), obese (≥95th percentile),
anxious or depressed, and learning problems at follow-up were assessed
according to baseline sleep categories.
Results: Children with very short sleep had higher odds of being obese
(OR = 3.3, P=0.03) and anxious or depressed (OR = 4.2, P=0.03) at
follow-up compared to children with normal sleep. Hispanic children
had higher odds for obesity (OR = 2.4, P = 0.01) than Caucasian children.
Borderline significance for overweight/obese (OR = 2.2, P=0.06)
and having learning problems (OR = 7.1, P=0.08) were seen for children
with very short sleep. A mean increase in BMI of 1.7 kg/m2 over the 5
years of follow-up (P=0.01) was seen for very short sleepers compared
to normal sleepers.
Conclusion: Children with very short sleep (< 7.5 hours/day) had an
increased risk for higher body weight in early adolescence; this risk was
higher for Hispanic than Caucasian children. Children with very short
sleep also had higher risk of being anxious or depressed or having learning
problems in early adolescence.
Support (If Any): The TuCASA study was supported by NHLBI grant
HL 62373.
0060
HIPPOCAMPAL VOLUME AND SLEEP IN CHILDREN OF
ALCOHOLICS
Hairston IS 1 , Cummiford CM 2 , Conroy DA 1 , Zubieta J 2,3 , Zucker RA 1 ,
Heitzeg M 1,2
1
Substance Abuse Section, Psychiatry, University of Michigan, Ann
Arbor, MI, USA, 2 Molecular and Behavioral Neuroscience Institute,
University of Michigan, Ann Arbor, MI, USA, 3 Psychiatry, University
of Michigan, Ann Arbor, MI, USA
Introduction: Mounting evidence suggests that sleep plays a role in
neural plasticity, especially of the hippocampus, which is sensitive to
neurotrophic or stressful signals. Although not a universal finding, several
studies report that insomnia and sleep-related disordered breathing,
in adults, is associated with smaller hippocampal volume. Similarly,
evidence from animal studies suggests that sleep is involved in hippocampal
neurogenesis and synaptic density, in both adult and developing
brains. In this study we assessed the relationship between subjective and
objective sleep measurements, behavioural problems, and gray matter
volume in children of alcoholic (COA) parents, hypothesizing that sleep
disruption will be associated with cortical and hippocampal development,
reflected by gray matter volumes.
Methods: 31 children of alcoholic parents, ages 8-12 (15 girls, 16
boys), wore actiwatches and completed sleep diaries for one week, and
their parents completed the Paediatric Sleep Questionnaire (PSQ). T1-
weighted, high-resolution, magnetic resonance images were obtained
from each child. Cortical volume analysis was performed using Free-
Surfer software. Teacher-rated internalizing (In) and externalizing (Ex)
problem scores were obtained. Sleep variables and behaviour variables
were correlated with the total cortical and white matter volume, and with
hippocampal and amygdala volumes.
Results: Younger children reported more wake after sleep onset
(WASO: p=.035), which coincided with an age-dependent decline in
parent-reported insomnia (p=.046). Age and gender were not associated
with actigraphy measures. Actigraphy total sleep time (TST) and sleep
efficiency correlated with Ex scores (R2=-.505, R2=-.505), with no cor-
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SLEEP, Volume 34, Abstract Supplement, 2011