Postnatal behavioural and inflammatory alterations in female pups prenatally exposed to valproic acid

KAZLAUSKAS N; CAMPOLONGO M; LUCCHINA L; ZAPPALA C; DEPINO AM

PSYCHONEUROENDOCRINOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2016 vol. 72 p. 11 - 21

0306-4530

In Autism Spectrum Disorders (ASD), a bias to a higher incidence in boys than in girls has been reported.With the aim to identify biological mechanisms acting in female animals that could underlie this bias,we used an extensively validated mouse model of ASD: the prenatal exposure to valproic acid (VPA). Wefound postnatal behavioral alterations in female VPA pups: a longer latency in righting reflex at postnatalday (P) 3, and a delay in the acquisition of the acoustic startle response. We also analyzed the densityof glial cells in the prefrontal cortex, hippocampus and cerebellum, in VPA and control animals. FemaleVPA pups showed alterations in the density of astrocytes and microglial cells between P21 and P42, withspecific dynamics in each brain region. We also found a decrease in histone 3 acetylation in the cerebellumof female VPA pups at P14, suggesting that the changes in glial cell density could be due to alterationsin the epigenetic developmental program. Finally, no differences in maternal behavior were found. Ourresults show that female VPA pups exhibit behavioral and inflammatory alterations postnatally, althoughthey have been reported to have normal levels of sociability in adulthood. With our work, we contributeto the understanding of biological mechanisms underlying different effects of VPA on male and femalerodents, and we hope to help elucidate whether there are factors increasing susceptibility to ASD in boys and/or resilience in girls.