Ontogenesis of the Response to Sleep Loss
It is estimated that 30-35% of adults in the United States and other developed countries regularly get less than the recommended amount of sleep, which is generally considered to be 7-9 hours per night for adults. Lack of sleep can be caused by a variety of factors, including chronic insomnia, certain illnesses, and lifestyle habits such as night shifts or even frequent travel through different time zones. Lack of sleep can have a number of negative effects on the body and brain, including fatigue, irritability, difficulty concentrating, and increased risk of accidents and diseases such as obesity, diabetes, and also heart disease.
And what happens when children and teenagers don't get enough sleep? A new study provides insights into what's happening in the brain.
Are you sleeping enough? And what actually happens when you don't?
It is estimated that 30-35% of adults in the United States and other developed countries regularly get less than the recommended amount of sleep, which is generally considered to be 7-9 hours per night for adults. In addition, an estimated 10-15% of people in the general population suffer from chronic insomnia, which is difficulty falling asleep or staying asleep through at least three nights per week for a period of at least three months.
Lack of sleep can be caused by a variety of factors, including chronic insomnia, certain illnesses, and lifestyle habits such as night shifts or even frequent travel through different time zones. Lack of sleep can have a number of negative effects on the body and brain, including fatigue, irritability, difficulty concentrating, and increased risk of accidents and diseases such as obesity, diabetes, and also heart disease.
And what happens when mammal children and teenagers don't get enough sleep? A new study provides insights into what's happening in the brain.
The most important in a nutshell
This study investigates the effects of sleep deprivation (SD) on cortical RNA expression in developing mice. Using RNA sequencing, the study identifies functional gene categories that are specifically impacted by SD at different developmental stages. The study finds that the effects of SD on gene expression in the prefrontal cortex vary depending on age, with gene expression differences falling into three categories:
present at all ages,
present when mature sleep homeostasis is emerging,
and those specific to certain ages in adults
The researchers suggests that the Wnt-signaling pathway is a core mechanism regulated by sleep and that younger ages are more affected by genes related to growth and development, while changes in genes related to metabolism are specific to the effect of SD in adults. They also find that the third and fourth week after birth may be a period of vulnerability to disruption of plasticity pathways important for critical periods.
Overall, our main findings are that SD has dramatically different effects on PFC gene expression at different postnatal ages, and that the 3rd-4th postnatal week (≈ P24) may be a period of vulnerability to disruption of plasticity pathways important for CPs. This suggests that sleep serves conserved functions across development, and different functions depending on postnatal age.
Deep dive
Methods
How did the researchers approach it? In this study, male mice were used to investigate the effects of SD on brain gene expression across different postnatal development stages. The mice were housed under a 12:12 hour light-dark cycle, with food and water at will. Adult mice (10-12 weeks old) and 16, 24 and 30 days old mice were used in the study. They were housed separately and divided into two groups, sleep deprived and home cage controls.
The sleep deprivation was performed by keeping the mice awake using gentle handling techniques. Upon completion of sleep deprivation, the mice were euthanized, and the prefrontal cortex was dissected for RNA extraction. RNA sequencing was performed. The data was analyzed using various bioinformatics tools to study the gene expression changes across different development stages.
Animals were divided into 2 groups; sleep deprived (SD), and home cage controls (HC),
n=5-8 independent animals per group. HC control mice were left undisturbed and were
euthanized either 3h (P16, P24, P30) or 5h (P90) after light onset (ZT3, ZT5).
Findings
In this first study to investigate the effects of SD on cortical RNA expression across postnatal development the researchers found that there is a small set of differentially expressed genes after sleep deprivation present at all developmental ages. The Wnt-signaling pathway was significantly enriched. This is the first time that sleep deprivation has been shown to affect components of this essential signaling pathway. Wnt-signalling has a precise spatio-temporal organization defined by the combination of the Wnt ligands and frizzled receptors. The specific downregulation of certain genes suggests a key function for these elements in regulating neuronal activity during prolonged wakefulness.
What else do we learn from the study? First, a a core and developmentally conserved function of sleep is the regulation of neuroprotective mechanisms. Second, the underlying reasons for the change in sleep homeostasis during development may be revealed by molecular analyses such as this one. Third, the cortex of juvenile mice (so called P24-mice) is particularly sensitive to sleep loss, which overlaps with critical periods in the brain's development. Furthermore, sleep deprivation has a small effect on prefrontal cortex gene expression in the youngest group of animals (P16). In the adult brain, sleep deprivation induces changes that are related to energy metabolism.