ИСТИНА

Developing brain is highly vulnerable to hypoxic stress which can cause irreversible changes in adult brain function including signal transduction. The most widely represented excitatory signaling system in CNS is glutamatergic. The aim of our investigation was to check the existence of glutamatergic deficit in rat brain exposed to prenatal hypoxia on different time points of postnatal development and its effect on behavior. To model prenatal hypoxic stress in our laboratory we exposed rats to hypobaric hypoxia on the 14-16 days of pregnancy (180 Torr, 5 % O2, 3 hours). Chosen time point represents the beginning of cell proliferation and migration in hippocampal region. This period is also critical for establishment of metabolic glutamatergic signal transduction due to the fact that 2-weeks and 3-month old rats demonstrate higher amounts of IP3 and IP3R1-positive cells under exposure to prenatal hypoxia. Application of glutamate to acute slices causes stronger increase of IP3 level in hypoxic animals of both ages. These facts evidence the overactivation of intracellular component of group 1 mGluR-associated (ImGluR) signaling in both juvenile and adult rats. Overactivation of ImGluR signaling can be explained as compensation of decreased glutamate amount in hypoxia-exposed rats that is present during 1,5 years of postnatal development. On the behavioral level we observe decreased learning memory in rats exposed to prenatal hypoxia which can be connected to glutamatergic deficit of hippocampus in these animals. This hypothesis is supported by the fact that agonists of ImGluR correct learning memory in rats exposed to prenatal hypoxia. Scientific research was performed with involvement of the Research park of St. Petersburg State University Observatory of Environmental Safety Center and Centre for Molecular and Cell Technologies. The work was supported by RFBR grant no. 17-04-01118.