Central AMPK contributes to sleep homeostasis in mice.
AMP-activated protein kinase (AMPK) is an energy-sensing molecular signal involved in glucose and lipid metabolism. The known interaction of sleep with energy metabolism led us to investigate the role of central AMPK in sleep homeostasis. Sleep deprivation (SD) for 6 h increased p-AMPK protein in the hypothalamus and also increased the mRNA level of Ca(2+)/calmodulin (CaM)-dependent protein kinase kinase beta (CaMKK2), an activator of AMPK, and carnitine palmitoyltransferase 1 (CPT1), a downstream signaling factor of AMPK. Central injection of compound C (CC), an inhibitor of AMPK, suppressed EEG delta power during NREM sleep, while 5-aminoimidazole-4-carboxamide riboside (AICAR), an activator of AMPK, enhanced EEG delta power. The treatment of both CC and AICAR attenuated rebound responses of delta power in NREM sleep after SD. These results indicate that central AMPK is involved in the regulation of sleep depth and sleep homeostasis.
Chikahisa
Sachiko
S
Department of Integrative Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Fujiki
Nobuhiro
N
Kitaoka
Kazuyoshi
K
Shimizu
Noriyuki
N
Séi
Hiroyoshi
H
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology; D003700:Delta Rhythm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology
D002491:Central Nervous System Agents; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D012333:RNA, Messenger; D012265:Ribonucleotides; C516138:dorsomorphin; D000620:Aminoimidazole Carboxamide; D002334:Carnitine O-Palmitoyltransferase; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; C517700:Camkk2 protein, mouse; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide