Sleep deprivation induces the unfolded protein response in mouse cerebral cortex
Article first published online: 4 FEB 2005
Journal of Neurochemistry
Volume 92, Issue 5, pages 1150–1157, March 2005
How to Cite
Naidoo, N., Giang, W., Galante, R. J. and Pack, A. I. (2005), Sleep deprivation induces the unfolded protein response in mouse cerebral cortex. Journal of Neurochemistry, 92: 1150–1157. doi: 10.1111/j.1471-4159.2004.02952.x
- Issue published online: 4 FEB 2005
- Article first published online: 4 FEB 2005
- Received August 27, 2004; revised manuscript received October 21, 2004; accepted October 22, 2004.
- unfolded protein response
Little is known about the molecular mechanisms underlying sleep. We show the induction of key regulatory proteins in a cellular protective pathway, the unfolded protein response (UPR), following 6 h of induced wakefulness. Using C57/B6 male mice maintained on a 12:12 light/dark cycle, we examined, in cerebral cortex, the effect of different durations of prolonged wakefulness (0, 3, 6, 9 and 12 h) from the beginning of the lights-on inactivity period, on the protein expression of BiP/GRP78, a chaperone and classical UPR marker. BiP/GRP78 expression is increased with increasing durations of sleep deprivation (6, 9 and 12 h). There is no change in BiP/GRP78 levels in handling control experiments carried out during the lights-off period. PERK, the transmembrane kinase responsible for attenuating protein synthesis, which is negatively regulated by binding to BiP/GRP78, is activated by dissociation from BiP/GRP78 and by autophosphorylation. There is phosphorylation of the elongation initiation factor 2α and alteration in ribosomal function. These changes are first observed after 6 h of induced wakefulness. Thus, prolonging wakefulness beyond a certain duration induces the UPR indicating a physiological limit to wakefulness.