Peculiarities of DNA and Histone H3 Methylation in the Hippocampus and Neocortex of Rats Subjected to Pathological Treatments during the Prenatal Period

Tyulkova, E. I.; Vataeva, L. A.; Stratilov, V. A.; Barysheva, V S; Vetrovoy, O. V.

doi:10.1134/s1819712420010195

Cited by 6 publications

(2 citation statements)

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“…The prenatal severe hypobaric hypoxia (PSH) reported in our previous studies was used as a reliable model of maternal stress response during pregnancy [14, 15]. The animals used in the experiments were born from intact females and females exposed to 3 sessions of severe hypobaric hypoxia (SH) on the 14th, 15th, and 16th days of pregnancy (shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

Long-Term Effects of Prenatal Severe Hypoxia on Central and Peripheral Components of the Glucocorticoid System in Rats

et al. 2020

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Introduction: Prenatal hypoxia is a risk factor for the development of numerous neurological disorders. It is known that the maternal stress response to hypoxia determines the epigenetic impairment of the perinatal expression of glucocorticoid receptors (GR) in the hippocampus of the progeny, but so far no detailed study of how this affects the functional state of the glucocorticoid system during further ontogenesis has been performed. Objective: The goal of the present study was to examine the long-term effects of the prenatal hypoxia on the functioning of the glucocorticoid system throughout life. Methods: Prenatal severe hypobaric hypoxia (PSH) was induced in the critical period of embryonic hippocampal formation on days 14–16 of gestation in a hypobaric chamber (180 Torr, 5% oxygen, 3 h). The activity of central (hippocampus) and peripheral (liver) components of the glucocorticoid system was assessed in 1-day-old (newborn), 2-week-old (juvenile), 3-month-old (adult), and 18-month-old (aged) male rats. Results: The PSH resulted in continuously elevated baseline corticosterone blood levels in the adult and aged rats. The chronic elevation of the corticosterone levels was accompanied by a progressive deficit of the GR expression in the liver, increased hepatic glycogen content, dysregulated glucose-6-phosphatase activity, and eventually hypoglycemia. Elevated corticosterone appears to result from the impairment of the mechanisms of glucocorticoid negative feedback since a substantial decrease in both the total number of GR and their nuclear localization was observed already in the hippocampus of newborn rat pups and persisted throughout life. Corresponding stable hippocampal downregulation of GR-dependent genes was observed as well. Suppression of the maternal glucocorticoid stress response to hypoxia by metyrapone injection to pregnant rats prior to each hypoxic challenge considerably reduced corticosterone over-response to hypoxia and prevented reduced hippocampal GR. Conclusions: Our findings demonstrate that in progeny a deficit of hippocampal GR resulting from maternal glucocorticoid response to hypoxia remains stable throughout life and is accompanied by severe disturbances of baseline glucocorticoid levels and its peripheral reception. Negative consequences of PSH can be prevented by injection with an inhibitor of corticosterone synthesis (metyrapone) to pregnant females undergoing hypoxia.

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Section: Methodsmentioning

confidence: 99%

Long-Term Effects of Prenatal Severe Hypoxia on Central and Peripheral Components of the Glucocorticoid System in Rats

et al. 2020

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“…It led to disruption of the glucocorticoid negative feedback in the offspring and predetermining the development of a chronic depressive-like state associated with reduced plasticity of reactions to external stressors [26,27]. Whereas in a mature organism damaging effects lead the brain structures to malfunction, the pathological effects in the prenatal period cause perturbations in epigenetic tuning of the signaling systems of a developing organism [9,21,28,29]. However, it is still not completely clear whether the changes observed during pregnancy associated with hypoxia/ischemia, are due to the hypoxic factor itself or they are merely the outcomes of a nonspeci c stress response of a mother.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress accompanies HIF1-dependent impairment of glucose metabolism in the hippocampus of adult rats survived prenatal severe hypoxia

Vetrovoy,

Stratilov,

Potapova

et al. 2023

Preprint

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Many socially significant diseases are associated with disorders of prenatal development. Previously, we have shown the pathological role of hypoxia inducible factor HIF1 in post-hypoxic reoxygenation. This study aims to investigate the effect of prenatal severe hypoxia (PSH) on HIF1α protein expression as well as on HIF1-dependent activity of the pentose phosphate pathway (PPP) and anaerobic glycolysis in the hippocampus (HPC) of the offspring reached adulthood. We showed that PSH causes a stable increase in the content of HIF1α protein in the HPC which was accompanied by an increase in the efficacy of anaerobic glycolysis. This was testified by increased LDH activity and lactate concentration. At the same time, the amounts of G6PD, NADPH and also reduced glutathione decreased in the HPC of PSH rats, whereas the concentration of an oxidative stress marker, MDA, exceeded the control values. In a series of experiments using the model of emotional stress "learned helplessness" or the model of severe hypoxic stress, it was shown that in the HPC of control rats there was an increase in the amount of HIF1α in response to stress, which was also accompanied by more efficient anaerobic glycolysis and decreased efficacy of the PPP similar to the intact PSH rats. In the PSH rats, in turn, emotional stress resulted even in higher HIF1α levels without affecting glycolysis and PPP. Therefore, the increased content and activity of the transcription factor HIF1α in the HPC of adult rats exposed to prenatal hypoxia leads to the imbalance between glycolysis and the PPP which is accompanied by oxidative stress.

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Age-Associated Changes in Exploratory Activity in the Open Field Test in Rats Surviving Prenatal Hypoxia

Stratilov

Vetrovoy

Vataeva³

et al. 2022

Neurosci Behav Physi

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Peculiarities of DNA and Histone H3 Methylation in the Hippocampus and Neocortex of Rats Subjected to Pathological Treatments during the Prenatal Period

Cited by 6 publications

References 48 publications

Long-Term Effects of Prenatal Severe Hypoxia on Central and Peripheral Components of the Glucocorticoid System in Rats

Long-Term Effects of Prenatal Severe Hypoxia on Central and Peripheral Components of the Glucocorticoid System in Rats

Oxidative stress accompanies HIF1-dependent impairment of glucose metabolism in the hippocampus of adult rats survived prenatal severe hypoxia

Age-Associated Changes in Exploratory Activity in the Open Field Test in Rats Surviving Prenatal Hypoxia

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