Abstract
Widespread sleep deprivation is a continuing public health problem in the United States and worldwide affecting adolescents and adults. Acute sleep deprivation results in decrements in spatial memory and cognitive impairments. The hippocampus is vulnerable to acute sleep deprivation with changes in gene expression, cell signaling, and protein synthesis. Sleep deprivation also has long lasting effects on memory and performance that persist after recovery sleep, as seen in behavioral studies from invertebrates to humans. Although previous research has shown that acute sleep deprivation impacts gene expression, the extent to which sleep deprivation affects gene regulation remains unknown. Using an unbiased deep RNA sequencing approach, we investigated the effects of acute sleep deprivation on gene expression in the hippocampus. We identified 1,146 genes that were significantly dysregulated following sleep deprivation with 507 genes upregulated and 639 genes downregulated, including protein coding genes and long non-coding RNAs not previously identified as impacted by sleep deprivation. Notably, genes significantly upregulated after sleep deprivation were associated with RNA splicing and the nucleus. In contrast, downregulated genes were associated with cell adhesion, dendritic localization, the synapse, and postsynaptic membrane. Furthermore, we found through independent experiments analyzing a subset of genes that three hours of recovery sleep following acute sleep deprivation was sufficient to normalize mRNA abundance for most genes, although exceptions occurred for some genes that may affect RNA splicing or transcription. These results clearly demonstrate that sleep deprivation differentially regulates gene expression on multiple transcriptomic levels to impact hippocampal function.
Highlights
Sleep deprivation is a widespread public health problem in the United States and countries around the globe [1]
Deep RNA sequencing reveals the extent of changes in gene expression induced in the hippocampus by acute sleep deprivation Previously researchers analyzed the impact of sleep deprivation on gene expression in the hippocampus using microarrays [25]; this approach had limitations in detection due to the microarray chip design, i.e., probes must be designed a priori that target specific anticipated transcripts
We investigated the effects of 5 h acute sleep deprivation starting at lights on using gentle handling to identify changes in gene expression in the hippocampus with deep RNA sequencing
Summary
Sleep deprivation is a widespread public health problem in the United States and countries around the globe [1]. Acute sleep deprivation results in cognitive impairments (reviewed in [5]), as well as the exacerbation of neuropsychiatric and mood disorders (reviewed in [6, 7]). The decrements in cognitive function and performance induced by acute sleep deprivation create an economic burden with decreased workplace productivity as well as increased accident risk encumbering public safety [8,9,10,11]. Acute sleep deprivation results in increased levels of amyloid-beta as well as increased levels of tau in cerebral spinal fluid and plasma, which are pathological markers associated with increased risk of Alzheimer’s disease [12, 13].
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