ИСТИНА

Prenatal hypoxia (PH) is one of the most common causes of developing brain pathologies. This study was aimed to analyze the characteristics of the glutamate system and behavior during early (2-week), adult (3-month) postnatal ontogenesis and in the process of aging (18-month) of rats subjected to hypoxic stress (5% O2, 3 h) during 14-16 days of prenatal development. We have shown progressive with age decrease in the amount of glutamate in the hippocampus of rats subjected to PH, which is accompanied by a decrease in the number of NeuN+ cells, as well as a decrease in long-term memory and learning ability in the Morris water maze. A gradual decrease in the amount of glutamate inversely correlates with, apparently, a compensatory increase in the levels of mGluR1, IP3R1 and polyphosphoinositides. At the same time, the use of mGluR1 agonists normalizes the cognitive ability of rats subjected to PH. 18-month animals subjected to PH demonstrate decreased activity of liver glucose-6-phosphatase, the product of glucocorticoid-dependent transcription. This enzyme contributes to increase of glucose blood level and thus to reaction of glutamate synthesis in the brain. Glucocorticoid receptor levels, similarly, decrease with age in rats subjected to PH. These results indicate a significant contribution of the dysfunction of the glutamatergic system to the formation of early aging caused by PH. The mechanism of glutamatergic deficit can be glucocorticoid-dependent. Scientific research was performed with involvement of the Research park of SPbU Observatory of Environmental Safety Center. The work was supported by RFBR grant no. 17-04-01118.