Separating the contribution of glucocorticoids and wakefulness to the molecular and electrophysiological correlates of sleep homeostasis.
OBJECTIVE
The sleep-deprivation-induced changes in delta power, an electroencephalographical correlate of sleep need, and brain transcriptome profiles have importantly contributed to current hypotheses on sleep function. Because sleep deprivation also induces stress, we here determined the contribution of the corticosterone component of the stress response to the electrophysiological and molecular markers of sleep need in mice.


METHODS
N/A SETTINGS: Mouse sleep facility.


METHODS
C57BL/6J, AKR/J, DBA/2J mice.


METHODS
Sleep deprivation, adrenalectomy (ADX).


RESULTS
Sleep deprivation elevated corticosterone levels in 3 inbred strains, but this increase was larger in DBA/2J mice; i.e., the strain for which the rebound in delta power after sleep deprivation failed to reach significance. Elimination of the sleep-deprivation-associated corticosterone surge through ADX in DBA/2J mice did not, however, rescue the delta power rebound but did greatly reduce the number of transcripts affected by sleep deprivation. Genes no longer affected by sleep deprivation cover pathways previously implicated in sleep homeostasis, such as lipid, cholesterol (e.g., Ldlr, Hmgcs1, Dhcr7, -24, Fkbp5), energy and carbohydrate metabolism (e.g., Eno3, G6pc3, Mpdu1, Ugdh, Man1b1), protein biosynthesis (e.g., Sgk1, Alad, Fads3, Eif2c2, -3, Mat2a), and some circadian genes (Per1, -3), whereas others, such as Homer1a, remained unchanged. Moreover, several microRNAs were affected both by sleep deprivation and ADX.


CONCLUSIONS
Our findings indicate that corticosterone contributes to the sleep-deprivation-induced changes in brain transcriptome that have been attributed to wakefulness per se. The study identified 78 transcripts that respond to sleep loss independent of corticosterone and time of day, among which genes involved in neuroprotection prominently feature, pointing to a molecular pathway directly relevant for sleep function.
Mongrain
Valérie
V
Center for Integrative Genomics, University of Lausanne, CH 1015 Lausanne, Switzerland.
Hernandez
Susana A
SA
Pradervand
Sylvain
S
Dorsaz
Stéphane
S
Curie
Thomas
T
Hagiwara
Grace
G
Gip
Phung
P
Heller
H Craig
HC
Franken
Paul
P
D000315:Adrenalectomy; D000818:Animals; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D005838:Genotype; D005938:Glucocorticoids / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000378:metabolism; D012892:Sleep Deprivation / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D014851:Wakefulness / Q000502:physiology*
D056925:Circadian Rhythm Signaling Peptides and Proteins; D005938:Glucocorticoids; D012333:RNA, Messenger; D003345:Corticosterone