Blog
About

  • Record: found
  • Abstract: found
  • Article: not found

Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Corticosterone, blood, Locus Coeruleus, metabolism, pathology, Male, Mice, Mice, Knockout, Mitochondria, genetics, Nerve Degeneration, Neurons, Oxidative Stress, physiology, Sirtuin 3, Sleep, Sleep Deprivation, Up-Regulation, Wakefulness, Animals

Read this article at

ScienceOpenPublisherPMC
Bookmark
      There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

      Abstract

      Modern society enables a shortening of sleep times, yet long-term consequences of extended wakefulness on the brain are largely unknown. Essential for optimal alertness, locus ceruleus neurons (LCns) are metabolically active neurons that fire at increased rates across sustained wakefulness. We hypothesized that wakefulness is a metabolic stressor to LCns and that, with extended wakefulness, adaptive mitochondrial metabolic responses fail and injury ensues. The nicotinamide adenine dinucleotide-dependent deacetylase sirtuin type 3 (SirT3) coordinates mitochondrial energy production and redox homeostasis. We find that brief wakefulness upregulates SirT3 and antioxidants in LCns, protecting metabolic homeostasis. Strikingly, mice lacking SirT3 lose the adaptive antioxidant response and incur oxidative injury in LCns across brief wakefulness. When wakefulness is extended for longer durations in wild-type mice, SirT3 protein declines in LCns, while oxidative stress and acetylation of mitochondrial proteins, including electron transport chain complex I proteins, increase. In parallel with metabolic dyshomeostasis, apoptosis is activated and LCns are lost. This work identifies mitochondrial stress in LCns upon wakefulness, highlights an essential role for SirT3 activation in maintaining metabolic homeostasis in LCns across wakefulness, and demonstrates that extended wakefulness results in reduced SirT3 activity and, ultimately, degeneration of LCns.

      Related collections

      Author and article information

      Journal
      24647961
      3960479
      10.1523/JNEUROSCI.5025-12.2014

      Comments

      Comment on this article