TY - JOUR

T1 - Paradoxical Anxiety Level Reduction in Animal Chronic Stress: A Unique Role of Hippocampus Neurobiology

AU - Tseilikman, Vadim

AU - Akulov, Andrey

AU - Shevelev, Oleg

AU - Khotskina, Anna

AU - Kontsevaya, Galina

AU - Moshkin, Mikhail

AU - Fedotova, Julia

AU - Pashkov, Anton

AU - Tseilikman, Olga

AU - Agletdinov, Eduard

AU - Tseilikman, David

AU - Kondashevskaya, Marina

AU - Zavjalov, Evgenii

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022/8/15

Y1 - 2022/8/15

N2 - A paradoxical reduction in anxiety levels in chronic predator stress paradigm (PS) in Sprague-Dawley rats has recently been shown in previous works. In this paper, we studied the possible neurobiological mechanism of this phenomenon. We segregated PS-exposed Sprague-Dawley rats into the high- and low-anxiety phenotypes. The long-lasting effects of PS on corticosterone levels, blood flow speed in the carotid arteries, diffusion coefficient, and 1H nuclear magnetic resonance spectra in the hippocampus were compared in the high-anxiety and low-anxiety rats. In addition, we evaluated the gene BDNF expression in the hippocampus which is considered to be a main factor of neuroplasticity. We demonstrated that in low-anxiety rats, the corticosterone level was decreased and carotid blood flow speed was increased. Moreover, in the hippocampus of low-anxiety rats compared to the control group and high-anxiety rats, the following changes were observed: (a) a decrease in N-acetyl aspartate levels with a simultaneous increase in phosphoryl ethanol amine levels; (b) an increase in lipid peroxidation levels; (c) a decrease in apparent diffusion coefficient value; (d) an increase in BDNF gene expression. Based on these findings, we proposed that stress-induced anxiety reduction is associated with the elevation of BDNF gene expression directly. Low corticosterone levels and a rise in carotid blood flow speed might facilitate BDNF gene expression. Meanwhile, the decrease in apparent diffusion coefficient value and decrease in N-acetyl aspartate levels, as well as an increase in the lipid peroxidation levels, in the hippocampus possibly reflected destructive changes in the hippocampus. We suggested that in Sprague-Dawley rats, these morphological alterations might be considered as an impetus for further increase in neuroplasticity in the hippocampus.

AB - A paradoxical reduction in anxiety levels in chronic predator stress paradigm (PS) in Sprague-Dawley rats has recently been shown in previous works. In this paper, we studied the possible neurobiological mechanism of this phenomenon. We segregated PS-exposed Sprague-Dawley rats into the high- and low-anxiety phenotypes. The long-lasting effects of PS on corticosterone levels, blood flow speed in the carotid arteries, diffusion coefficient, and 1H nuclear magnetic resonance spectra in the hippocampus were compared in the high-anxiety and low-anxiety rats. In addition, we evaluated the gene BDNF expression in the hippocampus which is considered to be a main factor of neuroplasticity. We demonstrated that in low-anxiety rats, the corticosterone level was decreased and carotid blood flow speed was increased. Moreover, in the hippocampus of low-anxiety rats compared to the control group and high-anxiety rats, the following changes were observed: (a) a decrease in N-acetyl aspartate levels with a simultaneous increase in phosphoryl ethanol amine levels; (b) an increase in lipid peroxidation levels; (c) a decrease in apparent diffusion coefficient value; (d) an increase in BDNF gene expression. Based on these findings, we proposed that stress-induced anxiety reduction is associated with the elevation of BDNF gene expression directly. Low corticosterone levels and a rise in carotid blood flow speed might facilitate BDNF gene expression. Meanwhile, the decrease in apparent diffusion coefficient value and decrease in N-acetyl aspartate levels, as well as an increase in the lipid peroxidation levels, in the hippocampus possibly reflected destructive changes in the hippocampus. We suggested that in Sprague-Dawley rats, these morphological alterations might be considered as an impetus for further increase in neuroplasticity in the hippocampus.

KW - anxiety

KW - BDNF

KW - hippocampus

KW - lipid peroxidation

KW - N-acetyl aspartate

KW - phosphoryl ethanol amine

KW - predator stress

UR - http://www.scopus.com/inward/record.url?scp=85137124303&partnerID=8YFLogxK

U2 - 10.3390/ijms23169151

DO - 10.3390/ijms23169151

M3 - Article

C2 - 36012411

AN - SCOPUS:85137124303

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 16

M1 - 9151

ER -