ИСТИНА

In this in vivo study using prenatal severe hypoxia (PSH) stress model we have shown that hypoxic sessions presented on the critical period of the embryonic hippocampal formation (days 14-16 of the gestation) lead to stable decrease of the glucocorticoid receptors (GR) expression in this brain structure of progeny. This effect associated with glucocorticoid stress response of mother. Decrease in both the total number of GR and their nuclear localization observed already in newborn rat pups and persists throughout life (2-week, 3- and 18- month time points of ontogenesis were studied), which lead to stable decrease in expression of the hippocampal GR-dependent genes. The decrease in GR-dependent transcription in the hippocampus promotes a violation of the extrahypothalamic glucocorticoid negative feedback regulation and increasing of the basal corticosterone (CS) levels in the blood plasma of the adult and aging animals. A chronic increase in CS levels causes an age-associated decrease in the liver GR content, leading to a decrease in G6Pase activity and hypoglycemia. In addition to the dysfunction of extrahypothalamic control of the glucocorticoid system, the impaired effectiveness of the glucocorticoid reception in the hippocampus disrupts the functioning of the glutamate mediator system through insufficient expression of glutamate metabolism genes, which is manifested in an age-associated decrease in the quantity of this mediator, weakening of cognitive functions of PSH rats, early neuronal loss and early mortality.