Sleep. 2010 Jul;33(7):889-900.

Changes in components of energy regulation in mouse cortex with increases in wakefulness.

Nikonova EV, Naidoo N, Zhang L, Romer M, Cater JR, Scharf MT, Galante RJ, Pack AI.

Source

Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-3403, USA.

Abstract

STUDY OBJECTIVES:

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.

DESIGN:

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.

PARTICIPANTS:

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

INTERVENTIONS:

3, 6, and 12 h of sleep deprivation.

MEASUREMENTS AND 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.