Cortistatin promotes and negatively correlates with slow-wave sleep.
Sleep need is characterized by the level of slow-wave activity (SWA) and increases with time spent awake. The molecular nature of this sleep homeostatic process is practically unknown. Here, we show that intracerebroventricular administration of the neuropeptide, cortistatin (CST-14), enhances EEG synchronization by selectively promoting deep slow-wave sleep (SWS) during both the light and dark period in rats. CST-14 also increases the level of slow-wave activity (SWA) within deep SWS during the first two hours following CST-14 administration. Steady-state levels of preprocortistatin mRNA oscillate during the light:dark cycle and are four-fold higher upon total 24-h sleep deprivation, returning progressively to normal levels after eight hours of sleep recovery. Preprocortistatin mRNA is expressed upon sleep deprivation in a particular subset of cortical interneurons that colocalize with c-fos. In contrast, the number of CST-positive cells coexpressing pERK1/2 decreases under sleep deprivation. The capacity of CST-14 to increase SWA, together with preprocortistatin's inverse correlation with time spent in SWS, suggests a potential role in sleep homeostatic processes.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Patrice
P
Bourgin
Véronique
V
Fabre
Salvador
S
Huitrón-Reséndiz
Steven J
SJ
Henriksen
Oscar
O
Prospero-Garcia
José R
JR
Criado
Luis
L
de Lecea
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003344:Cortical Synchronization / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology*
D009479:Neuropeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C099323:cortistatin; C107518:preprocortistatin; D048052:Mitogen-Activated Protein Kinase 3