Аннотация:The efects of prenatal hypoxia on neurodevelopment are predominantly associated with impaired maternal glucocorticoidstimulation of the fetus, which is "imprinted" in altered sensitivity of glucocorticoid reception in brain structures of ofspringand can afect brain plasticity during lifespan. This study aimed to investigate response of the brain glucocorticoid systemto mild stress (MS) in adult rats that survived prenatal severe hypoxia (PSH) on embryonic days 14-16. In response to MSthe control (but not PSH) rats demonstrate increased corticosterone levels, a decrease in exploratory activity and increasedanxiety. In the raphe nuclei of adult PSH rats the expression of glucocorticoid receptors (GR) is increased without changesin serotonin levels in comparison with the control. MS induces a decrease in GR expression accompanied by up-regulationof tryptophan hydroxylase 2 (tph2) and down-regulation of monoamine oxidase A (maoa) transcription in the raphe nucleiof both control and PSH groups. PSH also causes signifcant deviations in GR expression and GR-dependent transcriptionin the hippocampus, the medial prefrontal cortex, but not in the amygdala of rats. However, in response to MS, PSH ratsdemonstrate mild changes in their activity, while in control animals the MS-induced activity of the glucocorticoid systemin these brain structures is similar to intact PSH animals. Impaired activity of the glucocorticoid system in the extrahypothalamic brain structures of PSH rats is accompanied by increase in the hypothalamic corticotropin-releasing hormone(CRH) levels in comparison with the control regardless of MS. Synthesis of proopiomelanocortin (POMC) and release ofadrenocorticotropic hormone (ACTH) into the blood are decreased in response to MS in the pituitary of control rats, whichdemonstrates a negative glucocorticoid feedback mechanism. Meanwhile, in the pituitary of PSH rats reduced POMC levelswere found regardless of MS. Thus, prenatal hypoxia causes depression-like patterns in the brain glucocorticoid systemwith adverse reaction to mild stressors.