Systems genetics implicate the key mitochondrial gene Nrf1 in the build-up of sleep pressure in mice
Year: 2026
Type: preprint
Abstract: Individual differences in resilience to the impact of sleep deprivation (SD) imply genetic and molecular factors contributing to the cognitive and physiological dysregulation associated with increased sleep pressure. SD’s impact has, however, been studied mostly at one molecular levels and in one genetic background. Using the BXD mouse genetic reference population, we show that SD results in wide-spread alterations in chromatin accessibility in the cerebral cortex. We integrated these findings with genomic, transcriptomic, and phenotypic data to infer the genetic and gene-regulatory network of the SD response; SD-Net. SD-Net revealed a centralized early transcriptional response to SD with genetic variation influencing downstream factors, providing a conceptual model explaining the observed independent inheritance of distinct sleep phenotypes. SD-Net further identified Nrf1 as central regulator of sleep pressure. We could validate Nrf1’s role, but not that of Dnm1l, implicating mitochondrial biogenesis rather than fission in the intracellular processes governing sleep homeostasis.
Source: Research Square
Institution: University of Lausanne
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7163328455