Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder

Komelkova, Maria; Манухина, Е. Б.; Downey, H. Fred; Sarapultsev, Alexey; Черкасова, О. П.; Kotomtsev, Viacheslav; Platkovskiy, Pavel; Fedorov, S.; Sarapultsev, Petr; Tseilikman, Olga; Tseilikman, David; Tseĭlikman, Vadim

doi:10.3390/ijms21165900

Cited by 6 publications

(10 citation statements)

References 29 publications

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“…The conservativeness of high-anxiety rats might be connected to their metabolical state specifics. In our previous studies performed on Wistar rats [ 37 ], we also observed a lower variability in neuroendocrine changes in high-anxiety stressed rats compared with the low-anxiety group. At the same time, an interesting correlation was found between the level of anxiety and the level of microsomal oxidation, determined in vivo using the hexenal sleep test [ 37 ].…”

Section: Discussionsupporting

confidence: 60%

“…In our previous studies performed on Wistar rats [ 37 ], we also observed a lower variability in neuroendocrine changes in high-anxiety stressed rats compared with the low-anxiety group. At the same time, an interesting correlation was found between the level of anxiety and the level of microsomal oxidation, determined in vivo using the hexenal sleep test [ 37 ]. Additionally, animals with a long duration of hexenal sleep were considered slow metabolizers.…”

Section: Discussionsupporting

confidence: 60%

“…It is well in line with the findings of earlier studies [ 36 ]. A recent study indicated that chronic PS exposures were accompanied by a reduction in plasma CS levels in Wistar rats, and CS levels were decreased in low-anxiety rats more significantly than in high-anxiety rats [ 37 ]. This is also consistent with the results of other studies in Sprague–Dawley rats.…”

Section: Discussionmentioning

confidence: 99%

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

Tseĭlikman

Akulov

Shevelev

et al. 2022

IJMS

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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.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

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

Tseĭlikman

Akulov

Shevelev

et al. 2022

IJMS

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“…The comparison of corticosterone and testosterone levels in the blood serum demonstrated that the decrease in measured hormone levels of all rats exposed to stress ( Table 1 ). The reduction of corticosterone level is a generally accepted index of PTSD-like state development [ 6 , 10 , 12 , 13 ]. Nevertheless, the values of corticosterone levels in resistant rats were statistically higher than in sensitive ones ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Our previous experiment showed that rats later becoming sensitive to stress prior to stress modeling had a higher corticosterone level. We managed to determine that cytochrome P4503A-mediated metabolism of glucocorticoids was prevailing in stress-resistant animals, whereas the metabolism of stress-sensitive animals depended from 11β-hydroxysteroid dehydrogenase type 2 [ 13 ].…”

Section: Resultsmentioning

confidence: 99%

New Morphofunctional Criteria for Resistance Profile in Post-Traumatic Stress Disorder Models as Adrenal Dysfunction Trigger

et al. 2021

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For the first time in modeling posttraumatic stress disorder (PTSD), we have described the morphofunctional state of adrenal glands in Wistar rats resistant and sensitive to predator stress (rodent fear of the predator). Despite the evident signs of adrenal dysfunction in both phenotypes, we have discovered the thickening of undifferentiated cell zone and high indices of functional activity of stem cells in resistant animals, suggesting ample adaptation. The most important data demonstrate the direct relationship between the reduction of corticosterone and testosterone levels and adrenal dysfunction in PTSD models. The study results allow considering the adrenal stem cells as potential therapeutic targets.

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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

Tseĭlikman

Lapshin

Klebanov

et al. 2022

IJMS

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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.

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Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder

Cited by 6 publications

References 29 publications

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

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

New Morphofunctional Criteria for Resistance Profile in Post-Traumatic Stress Disorder Models as Adrenal Dysfunction Trigger

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

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