Dose-dependent effects of isoflurane on TrkB and GSK3β signaling: Importance of burst suppression pattern

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Abstract

Objectives: Deep burst-suppressing isoflurane anesthesia regulates signaling pathways connected with antidepressant responses in the rodent brain: activation of TrkB neurotrophin receptor and inhibition of GSK3 beta kinase (glycogen synthase kinase 3 beta). The main objective of this study was to investigate whether EEG (electroencephalogram) burst suppression correlates with these intriguing molecular alterations induced by isoflurane.

Methods: Adult male mice pre-implanted with EEG recording electrodes were subjected to varying concentrations of isoflurane (1.0-2.0% ad 20 min) after which medial prefrontal cortex samples were collected for molecular analyses, and the data retrospectively correlated to EEG ( + /- burst suppression).

Results: Isoflurane dose-dependently increased phosphorylation of TrkB(Y816), CREBS133 (cAMP response element binding protein), GSK3 beta(S9) and p70S6k(T412/S424). The time spent in burst suppression mode varied considerably between individual animals. Notably, a subset of animals subjected to 1.0-1.5% isoflurane showed no burst suppression. While p-GSK3 beta(S9), p-CREBS133 and p-p70S6k(T412/S424) levels were increased in the samples obtained also from these animals, p-TrkB(Y816) levels remained unaltered.

Conclusions: Isoflurane dose-dependently regulates TrkB and GSK3 beta signaling and dosing associated with therapeutic outcomes in depressed patients produces most prominent effects.

Original languageEnglish
JournalNeuroscience Letters
Volume694
Pages (from-to)29-33
Number of pages5
ISSN0304-3940
DOIs
Publication statusPublished - 16 Feb 2019
MoE publication typeA1 Journal article-refereed

Fields of Science

  • Anesthesia
  • Protein phosphorylation
  • EEG burst suppression
  • Electrocerebral silence
  • Antidepressant
  • GLYCOGEN-SYNTHASE KINASE-3
  • ELECTROCONVULSIVE SHOCK
  • NEUROTROPHIN RECEPTOR
  • MOUSE HIPPOCAMPUS
  • ACTIVATION
  • ANESTHESIA
  • BRAIN
  • PHOSPHORYLATION
  • NARCOTHERAPY
  • DEPRESSION
  • 317 Pharmacy
  • 3111 Biomedicine
  • 3112 Neurosciences

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