How Sex Plays a Role in the Body's Response to Sleep Deprivation

Researchers have a better understanding of sleep disruption—particularly in the realm of sex-specific differences and cellular dysfunction—and are developing new research to study the interplay between sleep and memory.

The findings were presented on Nov 14 at Neuroscience 2023, the annual meeting of the Society for Neuroscience.

Approximately one out of every three adults in the United States report not getting enough sleep. Despite years of research into sleep and memory, neuroscientists still do not fully understand the exact causes and mechanisms of sleep disorders. Ongoing research aims to uncover these causes and advance more effective treatments.

New findings show that:

Hormonal changes in female mice provide some resilience to acute sleep deprivation, compared with male mice.
In female rodents, astrocytes play a crucial role in mediating estrogen’s effects on sleep, adding evidence to estrogen’s role in sleep regulation.
Young adult mice exhibit degraded markers of memory and cell health when exposed to sleep disruption—suggesting that problems with how cells manage proteins (i.e., proteostasis) precede a decline in memory.
Cuttlefish skin pattern displays change during sleep following social interactions; this work contributes to understanding the interplay between sleep and memory.

“Why we sleep remains one of the major enigmas of neuroscience,” says Robert Greene, MD, PhD, professor of psychiatry and neuroscience at the University of Texas Southwestern Medical Center and moderator of the press conference, in a release. “Recent neuroscience research is beginning to uncover some of these secrets, including understanding the price of sleep loss on brain function. Further studies show the surprisingly gender-specific gateway to sleep in females and female resilience to sleep loss when sleep is curtailed. Finally, pioneering research on dream sleep may take a step forward with cephalopods, like cuttlefish, that wear their dreams on their skin, potentially providing a unique window into their dream content.”

Press Conference Summary

Three of these presentations focus on sleep disruption in rodents. Two presentations highlight sex-specific differences, specifically in females. The other rodent study analyzes restricted sleep and cellular changes in the brain. The last presentation offers a new model for study (the cuttlefish) and offers preliminary findings from that exploration.

Acute sleep deprivation results in sex-specific differences in gene regulation, abstract PSTR557.05

Even though it’s now understood that there are sex-specific behavioral differences in acute sleep deprivation, most molecular studies have included male animals only.
Researchers studied changes in gene expression following acute sleep deprivation in female mice and found that female mice were more resilient to changes in gene expression than male mice.
Researchers found changes in gene expression for 99 genes in female mice (but female mice had virtually no differences in proestrus stages) compared with more than 1,100 gene expression changes in male mice.

The role of median preoptic nucleus astrocytes in estradiol’s modulation of sleep, abstract PSTR557.18

In women, ovarian hormone changes have been highly associated with increases in sleep disruption, yet little is understood about how ovarian hormones, like estrogens, affect sleep.
When researchers inhibited astrocytes in the preoptic area of the brain (an area involved in sleep regulation) in female rats, they found that estrogen no longer regulated sleep patterns conversely, when these cells where excited estrogen-like effects on sleep were mimicked
These findings suggest that astrocytes may play a major role in mediating estrogen’s effects on sleep.

Sleeping less, learning less: The lasting effects of restricted sleep on cognitive performance and neuronal health in young mice, abstract NANO67.02

Researchers showed that chronic short sleep exposure (three days a week over eight weeks) in young mice led to worse performance on learning tasks.
Molecules related to memory and cell health (eg, BiP, BDNF, p-CREB) were also affected, leading to adaptive endoplasmic reticulum stress response in the brain.
These findings suggest that disrupted proteostasis (protein regulation within the cell) leads to cognitive decline.

Modulation of active sleep following salient social encounters in the cuttlefish Sepia bandensis, abstract PSTR095.10

Like humans, cuttlefish exhibit complex brain function, including memory, social cognition, and signatures of rapid eye movement (REM) sleep.
Researchers hypothesize that skin patterns observed during active sleep indicate signs of reactivations of prior social encounters, similar to “replay” in vertebrates’ brains.
Cuttlefish were exposed to social interactions and then observed in sleep. The cuttlefish displayed rapidly changing skin patterns that varied from baseline, which researchers hypothesize are the cuttlefish replaying the social interactions as they sleep. Scientists are now exploring how cuttlefish use these displays, how these observed variations differ, and what this can tell us about our own brains.