Changes in components of energy regulation in mouse cortex with increases in wakefulness.
OBJECTIVE
Increases in ATP production machinery have been described in brain after 3 h of sleep deprivation. Whether this is sustained with longer durations of extended wakefulness is unknown. We hypothesized that energy depletion could be a mechanism leading to difficulty maintaining wakefulness and assessed changes in components of the electron transport chain.


METHODS
Protein levels of key subunits of complexes IV and V of the electron transport chain (COXI, COXIV, ATP5B) and uncoupling protein 2 (UCP2) in isolated mitochondria by Westerns in mouse cerebral cortex after 3 and 12 h of sleep deprivation were compared to that in control mice. Activity of complex IV enzyme and relevant transcription factors-Nrf1, Nrf2 (Gabp), and phosphorylation of AMP-dependent kinase (AMPK)-were also assessed.


METHODS
8-10 week old C57BL/6J male mice (n = 91).


METHODS
3, 6, and 12 h of sleep deprivation.


RESULTS
After both 3 and 12 h of sleep deprivation, complex IV proteins and enzyme activity were significantly increased. The complex V catalytic subunit was significantly increased after 12 h of sleep deprivation only. Increased levels of UCP2 protein after 12 h of sleep deprivation suggests that there might be alterations in the ATP/AMP ratio as wakefulness is extended. That phosphorylation of AMPK is increased after 6 h of sleep deprivation supports this assertion. The increase in Nrf1 and Nrf2 (Gabp) mRNA after 6 h of sleep deprivation provides a mechanism by which there is up-regulation of key proteins.


CONCLUSIONS
There are complex dynamic changes in brain energy regulation with extended wakefulness.
Nikonova
Elena V
EV
Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3403, USA.
Naidoo
Nirinjini
N
Zhang
Lin
L
Romer
Micah
M
Cater
Jacqueline R
JR
Scharf
Matthew T
MT
Galante
Raymond J
RJ
Pack
Allan I
AI
D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012892:Sleep Deprivation / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D000071246:Uncoupling Protein 2; D014851:Wakefulness
D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D003576:Electron Transport Complex IV; C118888:AMP-dependent kinase (ATP-forming); D017856:Phosphotransferases (Phosphate Group Acceptor); C530489:ATP5b protein, mouse; D025261:Mitochondrial Proton-Translocating ATPases