TY - JOUR

T1 - Prenatal Hypoxia Triggers a Glucocorticoid-Associated Depressive-like Phenotype in Adult Rats, Accompanied by Reduced Anxiety in Response to Stress

AU - Stratilov, Viktor

AU - Potapova, Sofiya

AU - Safarova, Diana

AU - Tyulkova, Ekaterina

AU - Vetrovoy, Oleg

PY - 2024/5/28

Y1 - 2024/5/28

N2 - Fetal hypoxia and maternal stress frequently culminate in neuropsychiatric afflictions in life. To replicate this condition, we employed a model of prenatal severe hypoxia (PSH) during days 14-16 of rat gestation. Subsequently, both control and PSH rats at 3 months old were subjected to episodes of inescapable stress to induce learned helplessness (LH). The results of the open field test revealed an inclination towards depressive-like behavior in PSH rats. Following LH episodes, control (but not PSH) rats displayed significant anxiety. LH induced an increase in glucocorticoid receptor (GR) levels in extrahypothalamic brain structures, with enhanced nuclear translocation in the hippocampus (HPC) observed both in control and PSH rats. However, only control rats showed an increase in GR nuclear translocation in the amygdala (AMG). The decreased GR levels in the HPC of PSH rats correlated with elevated levels of hypothalamic corticotropin-releasing hormone (CRH) compared with the controls. However, LH resulted in a reduction of the CRH levels in PSH rats, aligning them with those of control rats, without affecting the latter. This study presents evidence that PSH leads to depressive-like behavior in rats, associated with alterations in the glucocorticoid system. Notably, these impairments also contribute to increased resistance to severe stressors.

AB - Fetal hypoxia and maternal stress frequently culminate in neuropsychiatric afflictions in life. To replicate this condition, we employed a model of prenatal severe hypoxia (PSH) during days 14-16 of rat gestation. Subsequently, both control and PSH rats at 3 months old were subjected to episodes of inescapable stress to induce learned helplessness (LH). The results of the open field test revealed an inclination towards depressive-like behavior in PSH rats. Following LH episodes, control (but not PSH) rats displayed significant anxiety. LH induced an increase in glucocorticoid receptor (GR) levels in extrahypothalamic brain structures, with enhanced nuclear translocation in the hippocampus (HPC) observed both in control and PSH rats. However, only control rats showed an increase in GR nuclear translocation in the amygdala (AMG). The decreased GR levels in the HPC of PSH rats correlated with elevated levels of hypothalamic corticotropin-releasing hormone (CRH) compared with the controls. However, LH resulted in a reduction of the CRH levels in PSH rats, aligning them with those of control rats, without affecting the latter. This study presents evidence that PSH leads to depressive-like behavior in rats, associated with alterations in the glucocorticoid system. Notably, these impairments also contribute to increased resistance to severe stressors.

KW - Amygdala/metabolism

KW - Animals

KW - Anxiety/metabolism

KW - Behavior, Animal

KW - Corticotropin-Releasing Hormone/metabolism

KW - Depression/metabolism

KW - Disease Models, Animal

KW - Female

KW - Fetal Hypoxia/metabolism

KW - Glucocorticoids/metabolism

KW - Helplessness, Learned

KW - Hippocampus/metabolism

KW - Hypoxia/metabolism

KW - Male

KW - Phenotype

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects/metabolism

KW - Rats

KW - Receptors, Glucocorticoid/metabolism

KW - Stress, Psychological/metabolism

KW - glucocorticoid system

KW - maternal stress

KW - prenatal hypoxia

KW - learned helplessness

UR - https://www.mendeley.com/catalogue/0ad046b3-c5cb-31fa-bced-b05356f453d5/

U2 - 10.3390/ijms25115902

DO - 10.3390/ijms25115902

M3 - Article

C2 - 38892090

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 11

M1 - 5902

ER -