Maternal immune activation by LPS triggers fetal immune response and cognitive impairment in adult life

Abstract

There is growing evidence that maternal infection during pregnancy results in acute and chronic changes in developmental context structure and function of the central nervous system (CNS) in the fetus. These changes increase the risk of premature birth, mental retardation and neuropsychiatric disorders such as autism, attention deficit disorder, major depressive disorder, bipolar disorder and schizophrenia. In this study we evaluated BBB integrity in the hippocampus and cortex at 6, 12 and 24 hours of the Wistar female pregnant after injection of LPS and the integrity of placental barrier in the structures placenta and fetus brain. Pregnant Wistar rat received an intraperitoneal injection of LPS (0.25 mg/Kg) or PBS on gestational day 15. At 6, 12, and 24h following MIA or PBS injections, pregnant dams were anesthetized. Brain fetus, placenta, and amniotic fluid were collected. Blood-brain barrier (BBB) and placental- barrier (PB) integrity were evaluated. On postnatal 55 offspring from MIA and PBS were subjected to the habituation to the open field and object recognition tasks. For the behavioural test, evaluated the influence of MIA on habituation memory, recognition memory and covered distance in the adulthood of prole of pregnant rats after the injection of LPS. Our study demonstrates that maternal LPS was able to break through the BBB of pregnant rats and offspring, generating cognitive deficits in offspring including locomotor disorders and reduced habituation capacity and recognition memory.