TY - JOUR

T1 - 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, Vadim

AU - Lapshin, Maxim

AU - Klebanov, Igor

AU - Chrousos, George

AU - Vasilieva, Maria

AU - Pashkov, Anton

AU - Fedotova, Julia

AU - Tseilikman, David

AU - Shatilov, Vladislav

AU - Manukhina, Eugenia

AU - Tseilikman, Olga

AU - Sarapultsev, Alexey

AU - Downey, H. Fred

N1 - Funding Information: Funding: With the financial support of the Foundation for Advanced Scientific Research of the Federal State Budgetary Educational Institution of Higher Education «Chelyabinsk State University», RFBR and Chelyabinsk Region #20-415-740011. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - 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.

AB - 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.

KW - 11-βHSD-1

KW - anxiety-like behavior

KW - corticosterone

KW - elevated plus maze

KW - MAO-A

KW - mathematical modeling

KW - norepinephrine

KW - post-traumatic stress disorder

KW - PSS

KW - Stress, Psychological/metabolism

KW - Anxiety/metabolism

KW - Corticosterone

KW - Rats

KW - 11-beta-Hydroxysteroid Dehydrogenases/metabolism

KW - Norepinephrine/metabolism

KW - Animals

KW - Behavior, Animal/physiology

KW - Monoamine Oxidase/metabolism

KW - Brain/metabolism

UR - http://www.scopus.com/inward/record.url?scp=85129119380&partnerID=8YFLogxK

U2 - 10.3390/ijms23094881

DO - 10.3390/ijms23094881

M3 - Article

C2 - 35563271

AN - SCOPUS:85129119380

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 9

M1 - 4881

ER -