Mothers’ Sleep Apnea may Change Their Male Offspring's Autism

Sleep apnea during pregnancy may increase the risk for brain and behavioral changes associated with autism, especially in male offsprings, according to a study in rats by Amanda Vanderplow, Michael Cahill, and their colleagues at the University of Wisconsin-Madison. These findings support evidence for a link between sleep apnea and neurodevelopmental disorders, and provide a possible mechanism for explaining the link. The results were published in the open-access journal PLOS Biology.

During episodes of sleep apnea, breathing is partially or completely interrupted, often with hundreds of timers per night, intermittent hypoxia, or decreased oxygenation in the blood.

Sleep apnea during pregnancy is associated with an increase in obesity, and in the third trimester it occurs in about 15% of uncomplicated pregnancies and more than 60% of high-risk pregnancies. Sleep apnea during pregnancy is known to be harmful to the newborn, but its effects on neurodevelopment have not been well studied.

The researchers subjected pregnant rats to intermittent low oxygen levels during times of rest, during the second half of their gestational period to investigate the impacts. The treatment induced hypoxia in the mothers, but (as expected) not in the fetuses.

Behavioral abnormalities in offspring were observed shortly after birth, including altered distressed vocal patterns in both males and females. Maternal hypoxia impaired cognitive and social functioning in males, but not females, both of which persisted into adulthood. Consequences include reduced work memory and longer-term memory storage and reduced interest in socially innovative situations.

These behavioral changes were accompanied by significant abnormalities in the density and morphology of the dendritic spinal cord, the development of neurons that receive and integrate signals from other neurons. In adolescents of both sexes, but much more in males, the density of dendritic spines was elevated compared to age-matched control animals, mainly due to the absence of vertebral "pruning" or reduction, which is important for the process beginning in childhood and for normal brain development. It is not clear how maternal hypoxia induced these changes in the fetus that did not experience hypoxia.

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“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 also told, “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.”

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The researchers found that the 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.

Source-Medindia