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.
| Language | English |
|---|---|
| Journal | Neuroscience Letters |
| Volume | 694 |
| Pages | 29-33 |
| Number of pages | 5 |
| ISSN | 0304-3940 |
| DOIs | |
| Publication status | Published - 16 Feb 2019 |
| MoE publication type | A1 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
}
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 journal › Article › Scientific › peer-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 -