Aging induced endoplasmic reticulum stress alters sleep and sleep homeostasis.
Alterations in the quality, quantity, and architecture of baseline and recovery sleep have been shown to occur during aging. Sleep deprivation induces endoplasmic reticular (ER) stress and upregulates a protective signaling pathway termed the unfolded protein response. The effectiveness of the adaptive unfolded protein response is diminished by age. Previously, we showed that endogenous chaperone levels altered recovery sleep in Drosophila melanogaster. We now report that acute administration of the chemical chaperone sodium 4-phenylbutyrate (PBA) reduces ER stress and ameliorates age-associated sleep changes in Drosophila. PBA consolidates both baseline and recovery sleep in aging flies. The behavioral modifications of PBA are linked to its suppression of ER stress. PBA decreased splicing of X-box binding protein 1 and upregulation of phosphorylated elongation initiation factor 2 α, in flies that were subjected to sleep deprivation. We also demonstrate that directly activating ER stress in young flies fragments baseline sleep and alters recovery sleep. Alleviating prolonged or sustained ER stress during aging contributes to sleep consolidation and improves recovery sleep or sleep debt discharge.
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA.
Marishka K
MK
Brown
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA.
May T
MT
Chan
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA.
John E
JE
Zimmerman
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA; Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Allan I
AI
Pack
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA.
Nicholas E
NE
Jackson
Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, PA, USA; Division of Sleep Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: naidoo@mail.med.upenn.edu.
Nirinjini
N
Naidoo
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D018832:Molecular Chaperones / Q000502:physiology; D010448:Peptide Initiation Factors / Q000378:metabolism; D010654:Phenylbutyrates / Q000494:pharmacology; D058767:Protein Unfolding; D015398:Signal Transduction / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D010448:Peptide Initiation Factors; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid
4-phenylbutyrate; Aging; Chaperone; Sleep; Sleep loss/ deprivation; Unfolded protein response