Activity-dependent brain-derived neurotrophic factor expression regulates cortistatin-interneurons and sleep behavior

Mol Brain. 2011 Mar 9:4:11. doi: 10.1186/1756-6606-4-11.

Abstract

Background: Sleep homeostasis is characterized by a positive correlation between sleep length and intensity with the duration of the prior waking period. A causal role for brain-derived neurotrophic factor (BDNF) in sleep homeostasis has been suggested, but the underlying mechanisms remain unclear. Cortistatin, a neuropeptide expressed primarily in a subset of cortical GABAergic interneurons, is another molecule implicated in sleep homeostasis.

Results: We confirmed that sleep deprivation leads to an increase in cortical cortistatin mRNA expression. Disruption of activity-dependent BDNF expression in a genetically modified mouse line impairs both baseline levels of cortistatin mRNA as well as its levels following sleep deprivation. Disruption of activity-dependent BDNF also leads to a decrease in sleep time during the active (dark) phase.

Conclusion: Our studies suggest that regulation of cortistatin-expressing interneurons by activity-dependent BDNF expression may contribute to regulation of sleep behavior.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Biomarkers / metabolism
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Circadian Rhythm / physiology
  • Electroshock
  • Gene Expression Regulation
  • Interneurons / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Promoter Regions, Genetic / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sleep / physiology*
  • Sleep Deprivation / genetics
  • Sleep Deprivation / physiopathology
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Neuropeptides
  • RNA, Messenger
  • cortistatin
  • gamma-Aminobutyric Acid