Homer1a is a core brain molecular correlate of sleep loss

Stéphanie Maret, Stéphane Dorsaz, Laure Gurcel, Sylvain Pradervand, Brice Petit, Corinne Pfister, Otto Hagenbuchle, Bruce F. O'Hara, Paul Franken, Mehdi Tafti

Research output: Contribution to journalArticlepeer-review

303 Scopus citations

Abstract

Sleep is regulated by a homeostatic process that determines its need and by a circadian process that determines its timing. By using sleep deprivation and transcriptome profiling in inbred mouse strains, we show that genetic background affects susceptibility to sleep loss at the transcriptional level in a tissue-dependent manner. In the brain, Homer1a expression best reflects the response to sleep loss. Time-course gene expression analysis suggests that 2,032 brain transcripts are under circadian control. However, only 391 remain rhythmic when mice are sleep-deprived at four time points around the clock, suggesting that most diurnal changes in gene transcription are, in fact, sleep-wake-dependent. By generating a transgenic mouse line, we show that in Homer1-expressing cells specifically, apart from Homer1a, three other activity-induced genes (Ptgs2, Jph3, and Nptx2) are overexpressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of Homer1a suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness.

Original languageEnglish
Pages (from-to)20090-20095
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number50
DOIs
StatePublished - Dec 11 2007

Keywords

  • Homeostasis
  • Microarray
  • Sleep deprivation
  • Sleep function
  • mRNA tagging

ASJC Scopus subject areas

  • General

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