title: Deep sleep and parietal cortex gene expression changes are related to cognitive deficits with age.
abstract: BACKGROUND
  Age-related cognitive deficits negatively affect quality of life and can presage serious neurodegenerative disorders. Despite sleep disruption's well-recognized negative influence on cognition, and its prevalence with age, surprisingly few studies have tested sleep's relationship to cognitive aging.
  
  
  METHODS
  We measured sleep stages in young adult and aged F344 rats during inactive (enhanced sleep) and active (enhanced wake) periods. Animals were behaviorally characterized on the Morris water maze and gene expression profiles of their parietal cortices were taken.
  
  
  RESULTS
  Water maze performance was impaired, and inactive period deep sleep was decreased with age. However, increased deep sleep during the active period was most strongly correlated to maze performance. Transcriptional profiles were strongly associated with behavior and age, and were validated against prior studies. Bioinformatic analysis revealed increased translation and decreased myelin/neuronal pathways.
  
  
  CONCLUSIONS
  The F344 rat appears to serve as a reasonable model for some common sleep architecture and cognitive changes seen with age in humans, including the cognitively disrupting influence of active period deep sleep. Microarray analysis suggests that the processes engaged by this sleep are consistent with its function. Thus, active period deep sleep appears temporally misaligned but mechanistically intact, leading to the following: first, aged brain tissue appears capable of generating the slow waves necessary for deep sleep, albeit at a weaker intensity than in young. Second, this activity, presented during the active period, seems disruptive rather than beneficial to cognition. Third, this active period deep sleep may be a cognitively pathologic attempt to recover age-related loss of inactive period deep sleep. Finally, therapeutic strategies aimed at reducing active period deep sleep (e.g., by promoting active period wakefulness and/or inactive period deep sleep) may be highly relevant to cognitive function in the aging community.
authors.affiliation: Department of Molecular and Biomedical Pharmacology, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Buechel
authors.forename: Jelena
authors.initials: J
authors.lastname: Popovic
authors.forename: James L
authors.initials: JL
authors.lastname: Searcy
authors.forename: Nada M
authors.initials: NM
authors.lastname: Porter
authors.forename: Olivier
authors.initials: O
authors.lastname: Thibault
authors.forename: Eric M
authors.initials: EM
authors.lastname: Blalock
mesh_terms: D000375:Aging / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003072:Cognition Disorders / Q000235:genetics* / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D004566:Electrodes; D020869:Gene Expression Profiling; D008297:Male; D018782:Maze Learning / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010296:Parietal Lobe / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D012894:Sleep Stages / Q000235:genetics* / Q000502:physiology*; D013686:Telemetry; D015854:Up-Regulation / Q000502:physiology