Astrocyte-derived adenosine is central to the hypnogenic effect of glucose

Sci Rep. 2016 Jan 12:6:19107. doi: 10.1038/srep19107.

Abstract

Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose, and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / pharmacology*
  • Animals
  • Arterioles / drug effects
  • Arterioles / physiology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Biosensing Techniques
  • Extracellular Space / chemistry
  • Glucose / pharmacology*
  • Male
  • Mice, Inbred C57BL
  • Models, Biological
  • Neurons / drug effects
  • Neurons / metabolism
  • Norepinephrine / pharmacology
  • Preoptic Area / drug effects
  • Preoptic Area / physiology
  • Receptor, Adenosine A2A
  • Sleep / drug effects*
  • Vasodilation / drug effects

Substances

  • Receptor, Adenosine A2A
  • Glucose
  • Adenosine
  • Norepinephrine