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

Research output: Contribution to journalArticleScientificpeer-review

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.

LanguageEnglish
JournalNeuroscience Letters
Volume694
Pages29-33
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

Cite this

@article{3db7a3bf3848423496285fc6ff211185,
title = "Dose-dependent effects of isoflurane on TrkB and GSK3β signaling: Importance of burst suppression pattern",
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.",
keywords = "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",
author = "Wiebke Theilmann and Alitalo, {Okko August} and Iris Yorke and Rantam{\"a}ki, {Tomi Pentti Johannes}",
year = "2019",
month = "2",
day = "16",
doi = "10.1016/j.neulet.2018.11.018",
language = "English",
volume = "694",
pages = "29--33",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier",

}

Dose-dependent effects of isoflurane on TrkB and GSK3β signaling: Importance of burst suppression pattern. / Theilmann, Wiebke; Alitalo, Okko August; Yorke, Iris; Rantamäki, Tomi Pentti Johannes.

In: Neuroscience Letters, Vol. 694, 16.02.2019, p. 29-33.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Dose-dependent effects of isoflurane on TrkB and GSK3β signaling: Importance of burst suppression pattern

AU - Theilmann, Wiebke

AU - Alitalo, Okko August

AU - Yorke, Iris

AU - Rantamäki, Tomi Pentti Johannes

PY - 2019/2/16

Y1 - 2019/2/16

N2 - 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.

AB - 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.

KW - Anesthesia

KW - Protein phosphorylation

KW - EEG burst suppression

KW - Electrocerebral silence

KW - Antidepressant

KW - GLYCOGEN-SYNTHASE KINASE-3

KW - ELECTROCONVULSIVE SHOCK

KW - NEUROTROPHIN RECEPTOR

KW - MOUSE HIPPOCAMPUS

KW - ACTIVATION

KW - ANESTHESIA

KW - BRAIN

KW - PHOSPHORYLATION

KW - NARCOTHERAPY

KW - DEPRESSION

KW - 317 Pharmacy

KW - 3111 Biomedicine

KW - 3112 Neurosciences

U2 - 10.1016/j.neulet.2018.11.018

DO - 10.1016/j.neulet.2018.11.018

M3 - Article

VL - 694

SP - 29

EP - 33

JO - Neuroscience Letters

T2 - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

ER -