Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.

Prenatal hypoxia, often accompanied by maternal glucocorticoid stress, can predispose offspring to neurological disorders in adulthood. If placental ischemia (PI) primarily reduces fetal oxygen supply, the maternal hypoxia (MH) model also elicits a pronounced fetal glucocorticoid exposure. Here, we compared MH and PI in rats to distinguish their unique and overlapping effects on embryonic and newborn brain development.

Prenatal Hypoxia Predisposes to Impaired Expression of the and Genes in Adult Rats without Affecting Acetylcholine Metabolism during Embryonic Development.

Previous studies have shown that the combined effect of fetal hypoxia and maternal stress hormones predetermines tendency to nicotine addiction in adulthood. This study in rats aimed to investigate the effect of prenatal severe hypoxia (PSH) on acetylcholine metabolism in the developing brain, as well as on expression of acetylcholine receptors and in both the developing brain and adult brain structures following nicotine consumption. In the developing brain of PSH rats, no changes were found in the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) or disturbances in the acetylcholine levels.

Prenatal Hypoxia Triggers a Glucocorticoid-Associated Depressive-like Phenotype in Adult Rats, Accompanied by Reduced Anxiety in Response to Stress.

Fetal hypoxia and maternal stress frequently culminate in neuropsychiatric afflictions in life. To replicate this condition, we employed a model of prenatal severe hypoxia (PSH) during days 14-16 of rat gestation. Subsequently, both control and PSH rats at 3 months old were subjected to episodes of inescapable stress to induce learned helplessness (LH).

The Prenatal Hypoxic Pathology Associated with Maternal Stress Predisposes to Dysregulated Expression of the chrna7 Gene and the Subsequent Development of Nicotine Addiction in Adult Offspring.

Introduction: Previous studies have shown that fetal hypoxia predisposes individuals to develop addictive disorders in adulthood. However, the specific impact of maternal stress, mediated through glucocorticoids and often coexisting with fetal hypoxia, is not yet fully comprehended.

Methods: To delineate the potential effects of these pathological factors, we designed models of prenatal severe hypoxia (PSH) in conjunction with maternal stress and prenatal intrauterine ischemia (PII).

Oxidative Stress Accompanies HIF1-Dependent Impairment of Glucose Metabolism in the Hippocampus of Adult Rats That Survived Prenatal Severe Hypoxia.

Introduction: Many socially significant diseases are associated with prenatal developmental disorders. Previously, we showed the pathological role of hypoxia-inducible factor-1 (HIF1) in post-hypoxic reoxygenation. This study aimed 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 offspring that reached adulthood.

Prenatal Hypoxia-Induced Adverse Reaction to Mild Stress is Associated with Depressive-Like Changes in the Glucocorticoid System of Rats.

The effects of prenatal hypoxia on neurodevelopment are predominantly associated with impaired maternal glucocorticoid stimulation of the fetus, which is "imprinted" in altered sensitivity of glucocorticoid reception in brain structures of offspring and can affect brain plasticity during lifespan. This study aimed to investigate response of the brain glucocorticoid system to mild stress (MS) in adult rats that survived prenatal severe hypoxia (PSH) on embryonic days 14-16. In response to MS the control (but not PSH) rats demonstrate increased corticosterone levels, a decrease in exploratory activity and increased anxiety.

Prenatal Hypoxia Affects Nicotine Consumption and Withdrawal in Adult Rats via Impairment of the Glutamate System in the Brain.

The role of damaging factors in the prenatal period as a basis for drug addiction in offspring is of great interest. In this study, we aim at deciphering the effects and possible mechanisms of prenatal severe hypoxia (PSH) on predisposition to nicotine addiction in adult rats. In PSH rats, we found an increasing tendency to nicotine consumption in the two-bottle choice test.

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

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.

Prenatal Hypoxia Induces Premature Aging Accompanied by Impaired Function of the Glutamatergic System in Rat Hippocampus.

Prenatal hypoxia is among leading causes of progressive brain pathologies in postnatal life. This study aimed to analyze the characteristics of the hippocampal glutamatergic system and behavior of rats in early (2 weeks), adult (3 months) and advanced (18 months) postnatal ontogenesis after exposure to prenatal severe hypoxia (PSH, 180 Torr, 5% O2, 3 h) during the critical period in the formation of the hippocampus (days 14-16 of gestation). We have shown an age-dependent progressive decrease in the hippocampal glutamate levels, a decrease of the neuronal cell number in the CA1 hippocampal region, as well as impairment of spatial long-term memory in the Morris water navigation task.

Pharmacological HIF1 Inhibition Eliminates Downregulation of the Pentose Phosphate Pathway and Prevents Neuronal Apoptosis in Rat Hippocampus Caused by Severe Hypoxia.

The pentose phosphate pathway (PPP) of glucose metabolism in the brain serves as a primary source of NADPH which in turn plays a crucial role in multiple cellular processes, including maintenance of redox homeostasis and antioxidant defense. In our model of protective mild hypobaric hypoxia in rats (3MHH), an inverse correlation between hypoxia-inducible factor-1 (HIF1) activity and mRNA levels of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP, was observed. In the present study, it was demonstrated that severe hypobaric hypoxia (SH) induced short-term upregulation of HIF1 alpha-subunit (HIF1α) in the hippocampal CA1 subfield and decreased the activity of G6PD.

Neuroprotective Mechanism of Hypoxic Post-conditioning Involves HIF1-Associated Regulation of the Pentose Phosphate Pathway in Rat Brain.

Post-conditioning is exposure of an injured organism to the same harmful factors but of milder intensity which mobilizes endogenous protective mechanisms. Recently, we have developed a novel noninvasive post-conditioning (PostC) protocol involving three sequential episodes of mild hypobaric hypoxia which exerts pronounced neuroprotective action. In particular, it prevents development of pathological cascades caused by severe hypobaric hypoxia (SH) such as cellular loss, lipid peroxidation, abnormal neuroendocrine responses and behavioural deficit in experimental animals.

Mild hypobaric hypoxia preconditioning up-regulates expression of transcription factors c-Fos and NGFI-A in rat neocortex and hippocampus.

Transcription factors c-Fos and NGFI-A encoded by immediate early genes largely participate in the biochemical cascade leading to genomically driven lasting adaptation by neurons to injurious exposures including hypoxia/ischemia. Present study was designed to examine the involvement of c-Fos and NGFI-A in the development of brain hypoxic tolerance induced by mild hypoxic preconditioning. Earlier we have reported that preconditioning by repetitive mild hypobaric hypoxia (MHH) considerably increases neuronal resistance to subsequent severe injurious exposures.