title: Recurrent Sleep Fragmentation Induces Insulin and Neuroprotective Mechanisms in Middle-Aged Flies.
abstract: Lack of quality sleep increases central nervous system oxidative stress and impairs removal of neurotoxic soluble metabolites from brain parenchyma. During aging poor sleep quality, caused by sleep fragmentation, increases central nervous system cellular stress. Currently, it is not known how organisms offset age-related cytotoxic metabolite increases in order to safeguard neuronal survival. Furthermore, it is not understood how age and sleep fragmentation interact to affect oxidative stress protection pathways. We demonstrate sleep fragmentation increases systems that protect against oxidative damage and neuroprotective endoplasmic reticulum molecular chaperones, as well as neuronal insulin and dopaminergic expression in middle-aged Drosophila males. Interestingly, even after sleep recovery the expression of these genes was still upregulated in middle-aged flies. Finally, sleep fragmentation generates higher levels of reactive oxygen species (ROS) in middle-aged flies and after sleep recovery these levels remain significantly higher than in young flies. The fact that neuroprotective pathways remain upregulated in middle-aged flies beyond sleep fragmentation suggests it might represent a strong stressor for the brain during later life.
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Williams
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Emelie
authors.initials: E
authors.lastname: Perland
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Mikaela M
authors.initials: MM
authors.lastname: Eriksson
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Josef
authors.initials: J
authors.lastname: Carlsson
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Erlandsson
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Loora
authors.initials: L
authors.lastname: Laan
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Tabusi
authors.initials: T
authors.lastname: Mahebali
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Ella
authors.initials: E
authors.lastname: Potter
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Frediksson
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.affiliation: Functional Pharmacology, Department of Neuroscience, Uppsala University Uppsala, Sweden.
authors.forename: Helgi B
authors.initials: HB
authors.lastname: Schiöth
keywords: Nrf2; dopamine; glucagon; insulin; metabolism; molecular chaperone; sleep