TY - JOUR
TI - The Link between Activities of Hepatic 11beta-Hydroxysteroid Dehydrogenase-1 and Monoamine Oxidase-A in the Brain Following Repeated Predator Stress: Focus on Heightened Anxiety
AU - Tseilikman, V.
AU - Lapshin, M.
AU - Klebanov, I.
AU - Chrousos, G.
AU - Vasilieva, M.
AU - Pashkov, A.
AU - Fedotova, J.
AU - Tseilikman, D.
AU - Shatilov, V.
AU - Manukhina, E.
AU - Tseilikman, O.
AU - Sarapultsev, A.
AU - Downey, H.F.
JO - International Journal of Molecular Sciences
PY - 2022
VL - 23
TODO - 9
SP - null
PB - MDPI
SN - 1422-0067
TODO - 10.3390/ijms23094881
TODO - 11beta hydroxysteroid dehydrogenase;  amine oxidase (flavin containing);  corticosterone;  noradrenalin, animal;  animal behavior;  anxiety;  brain;  mental stress;  metabolism;  physiology;  rat, 11-beta-Hydroxysteroid Dehydrogenases;  Animals;  Anxiety;  Behavior, Animal;  Brain;  Corticosterone;  Monoamine Oxidase;  Norepinephrine;  Rats;  Stress, Psychological
TODO - We investigated the presence of a molecular pathway from hepatic 11-βHSD-1 to brain MAO-A in the dynamics of plasma corticosterone involvement in anxiety development. During 14 days following repeated exposure of rats to predator scent stress for 10 days, the following variables were measured: hepatic 11-βHSD-1 and brain MAO-A activities, brain norepinephrine, plasma corticosterone concentrations, and anxiety, as reflected by performance on an elevated plus maze. Anxiety briefly decreased and then increased after stress exposure. This behavioral response correlated inversely with plasma corticosterone and with brain MAO-A activity. A mathematical model described the dynamics of the biochemical variables and predicted the factor(s) responsible for the development and dynamics of anxiety. In the model, hepatic 11-βHSD-1 was considered a key factor in defining the dynamics of plasma corticosterone. In turn, plasma corticosterone and oxidation of brain ketodienes and conjugated trienes determined the dynamics of brain MAO-A activity, and MAO-A activity determined the dynamics of brain norepinephrine. Finally, plasma corticosterone was modeled as the determinant of anxiety. Solution of the model equations demonstrated that plasma corticosterone is mainly determined by the activity of hepatic 11-βHSD-1 and, most importantly, that corticosterone plays a critical role in the dynamics of anxiety following repeated stress. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
ER -