Impact of hypoxic preconditioning on the alterations in phosphate-activated glutaminase activity in the brains of offspring

Abstract

The hypoxic preconditioning model is widely used in experimental studies to identify mechanisms for increasing the tolerance of organisms to subsequent hypoxic exposure. Glutaminase is the main enzyme that synthesizes glutamate, which has two important physiological roles: in the postnatal period, it acts as an excitatory neurotransmitter, and during the prenatal period, it regulates neurogenesis, synaptogenesis, and the survival of nerve cells. In our work, in 4 experimental groups, we investigated the effect of hypoxic preconditioning performed during days 16–21 of pregnancy on glutamate synthesis in the brains of 17-day-old and 6-month-old offspring. It was found that prenatal hypoxia led to a pronounced increase in the enzyme activity in various brain structures in early postnatal ontogenesis, while a decrease was observed in adult animals. In contrast, exposure to acute hypoxia resulted in a more significant increase in glutaminase activity in the brains of adult animals. Prenatal fetal hypoxic preconditioning caused a weakening effect on the increase in enzyme activity in 17-day-old rat offspring and a down-regulation in 6-month-olds, compared to the group that suffered acute hypoxia in the postnatal period. Thus, a neuroprotective adaptive-compensatory effect of prenatal preconditioning has been demonstrated, which can be associated with both the physiological and excitotoxic effects of glutamate.