Hippocampal neurogenic niche in mice perinatally exposed to ethanol

NERINA VILLALBA; CATALINA MADARNAS; ALICIA BRUSCO

Córdoba Capital

Congreso; IX INTERNATIONAL MEETING of the Latin American Society for Biomedical Research on Alcoholism; 2019

LASBRA

In humans, exposure to ethanol (EtOH) during pregnancy can cause serious alterations in morphological,behavioral and cognitive development in children which may also persist into adulthood. Children with Fetal Alcohol Syndrome (FAS) have shown distinctive, persistent and subtle patterns of cognitive dysfunction which become more pronounced with more complex psychological assessments. Previous studies in our laboratory demonstrated that rat prenatal EtOH exposure produces alterations in the morphological organization of the cerebral cortex which correlates with behavioral dysfunction. Given that adult neurogenesis has been recently postulated as a target for therapeutic approaches in neurological disorders, the aim of this work was to analyze the morphology and cytology of the neurogenic niches in the hippocampus of CD1 mice perinatally exposed to EtOH. Primiparous female CD1 mice were exposed to EtOH 6% v/v for four weeks previous to mating. Pregnant mice drank EtOH 6% v/v throughout pregnancy and during lactation.This model of maternal alcoholism rendered no significant differences between EtOH and control mice interms of weight gain or the number of offspring. Mothers yielded a blood ethanol concentration (BEC) of 73.29±8.69 mg/dl at the end of lactation, while pups yielded a BEC of 101.56±5.21 mg/dl at P21, which shows increasing BEC in pups as compared to mothers. At P21, male pups were separated, exposed to standard food and water ad libitum until adulthood and never exposed to EtOH for the rest of their lives. At P0, P21 and P80, pups were perfused with formaldehyde and brains were used for immunofluorescence studies. We analyzed the morphological evolution of the hippocampus through a mathematical approach measuring circularity, roundness, thickness and cellular composition of the dentate gyrus, a hippocampal neurogenic niche. While brains exposed to EtOH showed higher circularity and roundness than controls, the thickness of the granular layer was lower than controls and persisted until adulthood when an astrocytic reaction was present, even though animals were not exposed to EtOH after weaning.