Assessment of the transgenerational effect of valproic acid in mice

ZAPPALA C; CAMPOLONGO M; KAZLAUSKAS N; SEIFFE A; DEPINO A

Congreso; 2nd FALAN Congress; 2016

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction, and by restricted, repetitive and stereotyped behaviors. The exact causes of this disorder remain unclear. We and others have shown that mice prenatally exposed to valproic acid (VPA) at gestational day 12.5 (GD 12.5) show reduced social interaction and increased anxiety-related behavior in adulthood. Moreover, we recently found postnatal behavioral alterations in female VPA pups. VPA has multiple cellular effects, and so far it is unknown what is the mechanism by which it affects neural development. However, some studies suggest that its effect as an inhibitor of histone deacetylase activity may affect the expression of many genes and this, in turn, result in the brain developmental effects. We reasoned that this epigenetic mark could be transmitted across generations and it may affect the behavior of the offspring. The aim of this work was to study if the behavioral phenotype observed in mice prenatally exposed to VPA could be maternally transmited to the subsequent generation. We found postnatal behavioral alterations in the VPA F2, but no effects on social or anxiety-related behaviors in adulthood. Our results show that although some VPA effects can be epigenetically transmitted to the second generation by the mother, autism-related behaviors are not.