Fig 2.

Duration-dependent effects of sleep loss on locus coeruleus neurons (LCn). Short-term wakefulness (awake for three consecutive hours across the habitual sleep (lights-on) period) upregulates mitochondrial sirtuin type 3 (SirT3) activity, which then results in nuclear translocation of FoxO3a and transcriptional activation of anti-oxidants and PGC-1α to enhance mitochondrial biogenesis. In contrast, extended wakefulness (for 8 hours a day in the lights-on period for three consecutive days) reduces SirT3 protein and its NAD⁺-synthesizing enzymes, thereby reducing SirT3 activity and increasing mitochondrial acetylation of (and thereby inactivating) anti-oxidant enzymes, electron transport chain proteins, and FoxO3a. Mechanisms by which LCn switch from an adaptive to maladaptive response are not known.