Effects of Hypoxia or Dexamethasone at Different Gestation Periods on Fear Conditioning in Adult Rats

Vataeva, L. A.; Tyulkova, E. I.; Алехин, А. Н.; Stratilov, V. A.

doi:10.1134/s0022093018060030

Cited by 5 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%

“…Previously, we and other researchers have found that hypoxia during gestation leads to lasting disruption of motor, emotional, and research behavior as well as learning ability in the offspring, with corresponding changes in central nervous system functioning at both the molecular and cellular levels [2, 14-16]. As mentioned before, abnormalities of brain development caused by prenatal hypoxia are primarily determined by the maternal stress response to exogenous negative impacts [2, 17].…”

Section: Introductionmentioning

confidence: 96%

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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%