THE TRANSGENERATIONAL EFFECT OF MATERNAL HYPOXIA IN RATS IS MANIFESTED IN GLUCOCORTICOID-DEPENDENT DYSFUNCTION OF THE GLYMPHATIC SYSTEM AND COGNITIVE IMPAIRMENT

Hypoxia during pregnancy can have long-term negative effects on the health of the offspring. It is believed that maternal glucocorticoid stress plays a key role in disrupting normal brain development in the offspring, leading to neurological and endocrine pathologies in adulthood. These changes persist throughout life and can be passed on to future generations. This study aimed to investigate changes in the glucocorticoid and glymphatic systems in the brain of the offspring of female rats that experienced prenatal hypoxia.
The study was conducted on Wistar rats. On days 14-16 of pregnancy, the female rats were exposed to severe hypobaric hypoxia (three sessions of 3 hours each at 180 mmHg with 24-hour intervals between sessions). Intact males were introduced to control and prenatally hypoxic females at three months of age. Further studies were conducted on second-generation males.
Offspring of prenatally hypoxic females exhibited decreased exploratory activity and depressive-like behavior, as well as age-related decline in spatial memory. They were found to have increased POMC/ACTH levels in the pituitary gland, as well as increased corticosterone concentrations in the blood and hippocampus, accompanied by increased transcription of glucocorticoid-dependent upregulated genes and decreased mRNA and protein expression of the AQP4 and accumulation of beta-amyloid in the hippocampus.
Thus, the consequences of prenatal hypoxia have a negative impact even on the second generation, manifesting themselves in impaired glymphatic system function, depressive behavior, and spatial memory impairment, mediated by glucocorticoid hyperproduction.
This work was supported by the Russian Science Foundation (Project No. 25-75-10002).