Sleep is a basic human need, but many of us do not get nearly enough. In a new study, chemists combine proteomics and systems genetics to unpick how sleep deprivation negatively affects our cognitive function.
Sleep is critical in maintaining both physical and mental health. The amount that each person needs varies, but the CDC recommends at least seven hours a night for adults and more for children and babies—with school-age children and teens needing to clock up as many as 12 hours.1 Our natural circadian rhythms are attuned to a recurring day/night pattern, and many biological processes alter accordingly. But modern lifestyles often rob us of sleep, and in our 24/7 connected world, work and play can drive us to sleep later and wake earlier. Even if we are in bed, sleep may not be forthcoming, with stress and blue light technology often held accountable for chronic insomnia.
Acute sleep deprivation can often result in short-term cognitive dysfunction, which can interfere with work, driving, or social functioning the next day. Adults might experience this as fatigue or stress, whereas in children it can be masked by hyperactivity and poor attention span. But in the long term, chronic sleep loss causes damage to the central nervous system and increases the risk of neurodegenerative conditions such as Alzheimer’s or Parkinson’s disease. Until now, the detailed mechanisms by which sleep loss leads to cognitive dysfunction have been largely unknown, but a new study published in the Journal of Proteome Research aims to change that by harnessing the power of quantitative proteomics and systems genetics analysis.
A team of researchers in China used mass-spectrometry-based proteomics to show significant changes in protein expression in the brain. First, the team observed how successful mice were at navigating a maze and recognizing new objects after two days of no sleep. Then, they correlated the results with transcriptome-wide association screening to identify key regulators in the brain.2
They found that the sleep-deprived mice experienced a decline in pleiotrophin (PTN), a protein that has been studied in relation to the central nervous system and implicated in Alzheimer’s and other neurodegenerative diseases. Gene co-expression analysis further revealed the potential pathway in which decreased PTN secretion induced by insomnia leads to reduced binding on the postsynaptic membrane—ultimately causing brain cells in the hippocampus to die. The authors conclude that PTN levels could therefore be a promising indicator of cognitive impairment due to lack of sleep.
Omics approaches such as transcriptomics, proteomics, and metabolomics are increasingly being used to search for differential expression patterns. In addition to this study, researchers from this team have previously used proteomics to identify key regulators in prostate cancer progression,3 demonstrating the breath of application for these technologies.
- How much sleep do I need? Centers for Disease Control and Prevention, 2022.
- Zhou, Y. et al. The Combination of Quantitative Proteomics and Systems Genetics Analysis Reveals that PTN Is Associated with Sleep-Loss-Induced Cognitive Impairment. J. Proteome Res. 2023, 22, 9, 2936–2949.
- Zhang, Y. et al. Quantitative Proteomics of TRAMP Mice Combined with Bioinformatics Analysis Reveals That PDGF-B Regulatory Network Plays a Key Role in Prostate Cancer Progression. J. Proteome Res. 2018, 17, 7, 2401–2411.