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

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Theilmann , W , Alitalo , O A , Yorke , I & Rantamäki , T P J 2019 , ' Dose-dependent effects of isoflurane on TrkB and GSK3β signaling: Importance of burst suppression pattern ' , Neuroscience Letters , vol. 694 , pp. 29-33 . https://doi.org/10.1016/j.neulet.2018.11.018

Title: Dose-dependent effects of isoflurane on TrkB and GSK3β signaling: Importance of burst suppression pattern
Author: Theilmann, Wiebke; Alitalo, Okko August; Yorke, Iris; Rantamäki, Tomi Pentti Johannes
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
University of Helsinki, Division of Pharmacology and Pharmacotherapy
University of Helsinki, Drug Research Program
Date: 2019-02-16
Language: eng
Number of pages: 5
Belongs to series: Neuroscience Letters
ISSN: 0304-3940
URI: http://hdl.handle.net/10138/300098
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.
Subject: 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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