Chronic sleep deprivation induces alterations in DNA and RNA modifications by liquid chromatography-mass spectrometry analysis

Abstract

Sleep deprivation (SD) is a widespread issue that disrupts the lives of millions of people. These effects initiate as changes within neurons, specifically at the DNA and RNA level, leading to disruptions in neuronal plasticity and the dysregulation of various cognitive functions, such as learning and memory. Nucleic acid epigenetic modifications that could regulate gene expression have been reported to play crucial roles in this process. However, there is a lack of comprehensive research on the correlation of SD with nucleic acid epigenetic modifications. In the current study, we aimed to systematically investigate the landscape of modifications in DNA as well as in small RNA molecules across multiple tissues, including the heart, liver, kidney, lung, hippocampus, and spleen, in response to chronic sleep deprivation (CSD). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, we characterized the dynamic changes in DNA and RNA modification profiles in different tissues of mice under CSD stress. Specifically, we observed a significant decrease in the level of 5-methylcytosine (5mC) and a significant increase in the level of 5-hydroxymethylcytosine (5hmC) in the kidney in CSD group. Regarding RNA modifications, we observed an overall increased trend for most of these significantly changed modifications across six tissues in CSD group. Our study sheds light on the significance of DNA and RNA modifications as crucial epigenetic markers in the context of CSD-induced stress.