Sleep Deprivation and Neuronal Hyperexcitation Share Transcriptomic Signatures

Area of Science:

• Neuroscience
• Molecular Biology
• Genomics

Background:

• Sleep deprivation (SD) is linked to neuropsychiatric disorders, but its molecular basis is unclear.
• Extended wakefulness increases neuronal activity, suggesting a potential link between SD and neuronal hyperexcitation.

Purpose of the Study:

• To test if SD shares transcriptomic signatures with neuronal hyperexcitation.
• To identify gene pathways and cell types involved in these shared signatures.

Main Methods:

• Systematic comparison of publicly available transcriptomic datasets from SD and neuronal hyperexcitation models using the Running Fisher algorithm.
• Analysis across multiple mouse brain regions and rodent models.
• Single-cell transcriptomic analysis to identify enriched cell types.

Main Results:

• Significant transcriptomic overlaps (73%) were found between SD and neuronal hyperexcitation models.
• Shared signatures were enriched in pathways for neuronal plasticity, immune response, and inflammation.
• Key genes included immediate early genes (IEGs) and inflammation-associated genes.
• Microglia and neurons showed the strongest enrichment of shared signatures.

Conclusions:

• SD is associated with a transcriptomic state similar to acute neuronal hyperexcitation.
• Shared molecular pathways link sleep loss to processes implicated in neuropsychiatric disorders.
• Neuronal hyperexcitation molecular processes may contribute to SD-induced brain dysfunction.