Characterization of sevoflurane effects on Per2 expression using ex vivo bioluminescence imaging of the suprachiasmatic nucleus in transgenic rats

Neurosci Res. 2016 Jun;107:30-7. doi: 10.1016/j.neures.2015.11.010. Epub 2015 Dec 13.

Abstract

The inhalation anesthetic sevoflurane suppresses Per2 expression in the suprachiasmatic nucleus (SCN) in rodents. Here, we investigated the intra-SCN regional specificity, time-dependency, and pharmacological basis of sevoflurane-effects. Bioluminescence image was taken from the SCN explants of mPer2 promoter-destabilized luciferase transgenic rats, and each small regions of interest (ROI) of the image was analyzed. Sevoflurane suppressed bioluminescence in all ROIs, suggesting that all regions in the SCN are sensitive to sevoflurane. Clear time-dependency in sevoflurane effects were also observed; application during the trough phase of the bioluminescence cycle suppressed the subsequent increase in bioluminescence and resulted in a phase delay of the cycle; sevoflurane applied during the middle of the ascending phase induced a phase advance; sevoflurane on the descending phase showed no effect. These results indicate that the sevoflurane effect may depend on the intrinsic state of circadian machinery. Finally, we examined the involvement of GABAergic signal transduction in the sevoflurane effect. Co-application of both GABAA and GABAB receptor antagonists completely blocked the effect of sevoflurane on the bioluminescence rhythm, suggesting that sevoflurane inhibits Per2 expression via GABAergic signal transduction. Current study elucidated the anesthetic effects on the molecular mechanisms of circadian rhythm.

Keywords: Circadian rhythm; Ex vivo bioluminescence imaging; GABA-receptors; Sevoflurane; Suprachiasmatic nucleus.

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • GABA-A Receptor Antagonists / pharmacology
  • GABA-B Receptor Antagonists / pharmacology
  • Luminescent Measurements
  • Male
  • Methyl Ethers / pharmacology*
  • Molecular Imaging
  • Period Circadian Proteins / genetics
  • Period Circadian Proteins / metabolism*
  • Rats, Transgenic
  • Sevoflurane
  • Suprachiasmatic Nucleus / drug effects*
  • Suprachiasmatic Nucleus / metabolism

Substances

  • Anesthetics, Inhalation
  • GABA-A Receptor Antagonists
  • GABA-B Receptor Antagonists
  • Methyl Ethers
  • Per2 protein, rat
  • Period Circadian Proteins
  • Sevoflurane