Assessment of the transgenerational effect of valproic acid in mice

MARCOS CAMPOLONGO; AMAICHA DEPINO; NADIA KAZLAUSKAS; CECILIA ZAPPALA; ARACELI SEIFFE

Buenos Aires

Congreso; 2nd Federation of Latin American and Caribbean Neuroscience Societies Congress 2016; 2016

Autism spectrum disorder (ASD) is a neurodevelopmentaldisorder characterized by impairments in social interaction,and by restricted, repetitive and stereotyped behaviors.The exact causes of this disorder remain unclear. Weand others have shown that mice prenatally exposed tovalproic acid (VPA) at gestational day 12.5 (GD 12.5) showreduced social interaction and increased anxiety-relatedbehavior in adulthood. Moreover, we recently foundpostnatal behavioral alterations in female VPA pups. VPAhas multiple cellular effects, and so far it is unknown whatis the mechanism by which it affects neural development.However, some studies suggest that its effect as an inhibitorof histone deacetylase activity may affect the expressionof many genes and this, in turn, result in the braindevelopmental effects. We reasoned that this epigeneticmark could be transmitted across generations and it mayaffect the behavior of the offspring. The aim of this workwas to study if the behavioral phenotype observed in miceprenatally exposed to VPA could be maternally transmitedto the subsequent generation. We found postnatalbehavioral alterations in the VPA F2, but no effects on socialor anxiety-related behaviors in adulthood. Our results showthat although some VPA effects can be epigeneticallytransmitted to the second generation by the mother,autism-related behaviors are not.