Depressive-like behavior and impaired synaptic plasticity in the prefrontal cortex as later consequences of prenatal hypoxic-ischemic insult in rats

Abstract

Perinatal hypoxia-ischemia (HI) is a leading cause of morbidity and mortality among newborns. Infants with HI encephalopathy may experience lasting consequences, such as depression, in adulthood. In this study, we examined depressive-like behavior, neuronal population, and markers of monoaminergic and synaptic plasticity in the prefrontal cortex (PFC) of adolescent rats subjected to a prenatal HI model. Pregnant rats underwent a surgery in which uterine and ovarian blood flow was blocked for 45 min at E18 (HI procedure). Sham-operated subjects were also generated (SH procedure). Behavioral tests were conducted on male and female pups from P41 to P43, and animals were histologically processed or dissected for western blotting at P45. We found that the HI groups consumed less sucrose in the sucrose preference test and remained immobile for longer periods in the forced swim test. Additionally, we observed a significant reduction in neuronal density and PSD95 levels in the HI group, as well as a smaller number of synaptophysin-positive cells. Our results underscore the importance of this model in investigating the effects of HI-induced injuries, as it reproduces an increase in depressive-like behavior and suggests that the HI insult affects circuits involved in mood modulation.