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

Abstract

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.

Unveiling the Link: Exploring Mitochondrial Dysfunction as a Probable Mechanism of Hepatic Damage in Post-Traumatic Stress Syndrome

“…Previously, we reported the role of the liver in the allostatic response to experimental PTSD [ 43 ]. Liver damage in PTSD rats has also been recently reported [ 45 ].…”

“…GC deficiency has been associated with pathological overshoots of inflammatory responses. Usually, chronic stress is thought to increase plasma Cort concentration [ 7 , 46 ]; however, this PS model of PTSD is characterized by elevated GC metabolism in the liver due to an increase of 11βHSD1 activity [ 43 ]. Consequently, plasma Cort was reduced in the PS rats and significantly more so in the HA rats than in the LA rats.…”

“…Previously, we reported that chronic PS leads to a decrease in plasma Cort with a concomitant increase in proinflammatory cytokines [ 17 , 43 ]. These imbalances support the development of inflammation.…”

“…We have previously demonstrated an association between hepatic dysfunction and the development of anxiety disorders [ 43 ]. The results presented here have expanded our understanding of the hepatic factors involved in the development of anxiety and its manifestations.…”

Limited Cheese Intake Paradigm Replaces Patterns of Behavioral Disorders in Experimental PTSD: Focus on Resveratrol Supplementation

“…Additionally, an increase in hippocampal norepinephrine (NE) concentration has been observed. Interestingly, the activity and expression of monoamine oxidases (MAO), enzymes responsible for the oxidative deamination of monoamines, were found to be decreased in the hippocampus [ 23 ].…”