Conclusions
Isoflurane dose-dependently regulates TrkB and GSK3β signaling and dosing associated with therapeutic outcomes in depressed patients produces most prominent effects.
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 TrkBY816, CREBS133 (cAMP response element binding protein), GSK3βS9 and p70S6kT412/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-GSK3βS9, p-CREBS133 and p-p70S6kT412/S424 levels were increased in the samples obtained also from these animals, p-TrkBY816 levels remained unaltered. Conclusions: Isoflurane dose-dependently regulates TrkB and GSK3β signaling and dosing associated with therapeutic outcomes in depressed patients produces most prominent effects.