Mothers' sleep apnea may increase risk of autism-like changes in their
male offspring
Study in rats links intermittent hypoxia in pregnancy to lifelong
deficits

Date:
February 3, 2022
Source:
PLOS
Summary:
Sleep apnea in pregnancy may increase the risk for brain and
behavioral changes associated with autism, especially in males,
according to a study in rats.



FULL STORY ========================================================================== Sleep apnea in pregnancy may increase the risk for brain and behavioral
changes associated with autism, especially in males, according to a
study in rats by Amanda Vanderplow, Michael Cahill, and colleagues
at the University of Wisconsin-Madison, and publishing Feb. 3 in the open-access journal PLOS Biology. The findings support evidence in
humans of a link between sleep apnea and neurodevelopmental disorders,
and provide a potential mechanism to explain the link.


========================================================================== During episodes of sleep apnea, breathing is partially or completely interrupted, often hundreds of timers per night, causing intermittent
hypoxia, or decreased blood oxygenation. The incidence of sleep apnea
during pregnancy is on the rise, in line with the obesity epidemic,
and occurs in about 15% of uncomplicated pregnancies and more than 60%
of high-risk pregnancies by the third trimester. Sleep apnea during
pregnancy is known to have detrimental effects on the newborn, but the
impacts on neurodevelopment have not been well studied.

To investigate such impacts, the authors subjected pregnant rats to intermittent low oxygen levels during times of rest, during the second
half of their gestational period. The treatment induced hypoxia in the
mothers, but (as expected) not in the fetuses. Behavioral abnormalities
in the offspring were observed beginning shortly after birth, including
altered distress vocalization patterns in both males and females. Maternal hypoxia also impaired cognitive and social function in male, but not
female, offspring, both of which persisted into adulthood. Effects
included reduction in working memory and longer-term memory storage,
and reduced interest in socially novel situations.

These behavioral changes were accompanied by significant abnormalities in
the density and morphology of dendritic spines, the outgrowths on neurons
that receive and integrate signals from other neurons. In adolescents of
both sexes, but much more so in males, the density of dendritic spines
was elevated compared to age-matched control animals, an increase due
mainly to lack of spine "pruning," or reduction, a process that begins
in childhood and is critical for normal brain development. How maternal
hypoxia induced these changes in fetuses not themselves experiencing
hypoxia remains unclear.

The authors found that affected offspring had excessive activity of a
cell signaling pathway known as the mTOR pathway, a feature identified
in the cortex of humans with autism, and that treatment with rapamycin,
an mTOR inhibitor, partially mitigated the behavioral effects of maternal hypoxia in the offspring.

"To our knowledge, this is the first direct demonstration of the effects
of maternal intermittent hypoxia during gestation on the cognitive and behavioral phenotypes of offspring," Cahill says. "Our data provide
clear evidence that maternal sleep apnea may be an important risk factor
for the development of neurodevelopmental disorders, particularly in
male offspring." Cahill adds, "Based on clinical correlations, maternal
sleep apnea during pregnancy has been theorized to potentially increase
risk for autism diagnosis in her offspring; however, functional studies
are lacking. Here we show that sleep apnea during gestation produces
neuronal and behavioral phenotypes in rodent offspring that closely
resemble autism, and demonstrate the efficacy of a pharmacological
approach in fully reversing the observed behavioral impairments."
special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by PLOS. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Amanda M. Vanderplow, Bailey A. Kermath, Cassandra R. Bernhardt,
Kimberly
T. Gums, Erin N. Seablom, Abigail B. Radcliff, Andrea C. Ewald,
Mathew V.

Jones, Tracy L. Baker, Jyoti J. Watters, Michael E. Cahill. A
feature of maternal sleep apnea during gestation causes
autism-relevant neuronal and behavioral phenotypes in
offspring. PLOS Biology, 2022; 20 (2): e3001502 DOI:
10.1371/journal.pbio.3001502 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220203161154.htm

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