Scientists highlight negative impacts of sleep disruption on early brain development

Sleep deprivation in adults has long been shown to cause long-term physical and mental health problems, including but not limited to a weakened immune system, weight gain, depression and increased risk of dementia.

But why does lack of sleep have such serious consequences?

In fact, sleep plays a crucial role from the moment we are born. As babies, our brains still form the ends of neurons, called synapses, which are important in learning, attention, working memory and long-term memory. Sleep allows these neurons to develop and connect with each other, establishing brain functions for the rest of your life.

If this delicate but important process were disrupted, whether by constant awakening or separation anxiety, it could have long-lasting effects on the brain and behavior.

Now, a new study led by Sean Gay, a graduate student in the lab of Graham Diering, Ph.D., assistant professor in the Department of Cell Biology and Physiology at the UNC School of Medicine, has given us more information about how sleep loss during early life affects important parts of brain development – and can also increase the risk of developing autism spectrum disorder (ASD).

Their findings were published in Proceedings of the National Academy of Sciences.

“The unique effects of sleep loss during development are largely unexplored,” Diering said. “Our data shows that babies and children are more vulnerable to the negative effects of sleep disturbances. We also found that sleep loss during this crucial period may interact negatively with underlying genetic risk for autism spectrum disorder.”

Sleep disturbance and autism

Sleep problems are an important early indicator of brain growth problems and other neurodevelopmental disorders such as ASD, attention deficit hyperactivity disorder, and intellectual disability. Sleep disruption has been observed in >80% of people with ASD, but it is not yet known whether sleep disruption is a cause or consequence of ASD.

Diering has long studied how sleep strengthens synapses over time—a process called synaptic plasticity—and how a lack of sleep can contribute to cognitive and neurodegenerative disorders. If researchers could better understand the links between sleep and ASD, researchers and doctors could also make earlier diagnoses and propose new treatment strategies for the disease.

In 2022, the Diering lab sought to understand whether sleep disruption during early life could interact with an underlying genetic risk for ASD to cause lasting changes in adult behavior. Using mouse models, researchers found that sleep disruption during the third week of life (similar to age 1 to 2 years in humans) caused lasting deficits in social behavior in male mice that were genetically vulnerable to having ASD.

A Study on Sleep Recovery

The Diering lab wanted to explore these findings further, this time investigating how adult and developing mouse models compensate for sleep loss. Using specialized mouse houses with highly sensitive sensors, researchers were able to carefully track the mouse’s movements and breathing, allowing researchers to keep score of waking and sleeping states.

The researchers showed that when adult mouse models lost a significant amount of sleep, they compensated by increasing sleep later during their regular activity hours. Called “sleep catch-up,” this response allowed adults to “make up” for lost sleep.

Younger mice, on the other hand, did not fully recover from sleep. This confirmed the researcher’s hypothesis that younger rats might be more susceptible to the harmful effects of sleep deprivation. The researchers also observed that sleep deprivation in young mice completely impaired their performance on a memory learning task, while adults were much more resilient after sleep loss.

Next, the lab turned its attention to the effects of sleep and sleep deprivation on neuronal synapses, which mediate communication between neurons and are the main site for memory formation and storage. They are also well studied for their key role in benefiting sleep health.

Researchers performed a series of molecular analyzes to see how sleep deprivation affects synapses. Using cutting-edge protein analyses, they were able to map the protein composition and biochemical changes that affect synapses. The analysis showed that sleep deprivation in young mice, but not in adults, strongly affected synapse formation, a fundamental aspect of brain development.

“This now provides one of the largest and most comprehensive data sets to examine the molecular effects of sleep loss across the lifespan,” Diering said.

Future Treatment Paths for Autism

An ongoing mission of the laboratory, informed through the molecular work of this current study, is to develop next-generation sleep-based medicines that can be used in children. Rather than acting as a sedative, they hope to create a drug that can target synapses to restore sleep function rather than altering sleep behavior itself.

“Development is not something you can go back and do again,” Diering said. “Sleep is important throughout life and especially during development. Understanding what we know now will place greater emphasis on understanding sleep problems in ASD and could lead to an important therapeutic path forward for treating ASD and other developmental conditions.”