Homer1a is a core brain molecular correlate of sleep loss.
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.
Maret
Stéphanie
S
Center for Integrative Genomics and Lausanne DNA Array Facility, University of Lausanne, Génopode, CH-1015 Lausanne, Switzerland.
Dorsaz
Stéphane
S
Gurcel
Laure
L
Pradervand
Sylvain
S
Petit
Brice
B
Pfister
Corinne
C
Hagenbuchle
Otto
O
O'Hara
Bruce F
BF
Franken
Paul
P
Tafti
Mehdi
M
D000818:Animals; D001921:Brain / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D000072233:Homer Scaffolding Proteins; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606623:Homer1 protein, mouse; D012333:RNA, Messenger