title: Postnatal behavioral and inflammatory alterations in female pups prenatally exposed to valproic acid.
abstract: 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). We found postnatal behavioral alterations in female VPA pups: a longer latency in righting reflex at postnatal day (P) 3, and a delay in the acquisition of the acoustic startle response. We also analyzed the density of glial cells in the prefrontal cortex, hippocampus and cerebellum, in VPA and control animals. Female VPA pups showed alterations in the density of astrocytes and microglial cells between P21 and P42, with specific dynamics in each brain region. We also found a decrease in histone 3 acetylation in the cerebellum of female VPA pups at P14, suggesting that the changes in glial cell density could be due to alterations in the epigenetic developmental program. Finally, no differences in maternal behavior were found. Our results show that female VPA pups exhibit behavioral and inflammatory alterations postnatally, although they have been reported to have normal levels of sociability in adulthood. With our work, we contribute to the understanding of biological mechanisms underlying different effects of VPA on male and female rodents, and we hope to help elucidate whether there are factors increasing susceptibility to ASD in boys and/or resilience in girls.
authors.affiliation: Institute for Physiology, Molecular Biology and Neurosciences, CONICET-UBA, and Department of Physiology, Molecular and Cellular Biology, FCEyN, University of Buenos Aires, C1428EHA, Buenos Aires, Argentina.
authors.forename: Nadia
authors.initials: N
authors.lastname: Kazlauskas
authors.affiliation: Institute for Physiology, Molecular Biology and Neurosciences, CONICET-UBA, and Department of Physiology, Molecular and Cellular Biology, FCEyN, University of Buenos Aires, C1428EHA, Buenos Aires, Argentina.
authors.forename: Marcos
authors.initials: M
authors.lastname: Campolongo
authors.affiliation: Institute for Physiology, Molecular Biology and Neurosciences, CONICET-UBA, and Department of Physiology, Molecular and Cellular Biology, FCEyN, University of Buenos Aires, C1428EHA, Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Lucchina
authors.affiliation: Institute for Physiology, Molecular Biology and Neurosciences, CONICET-UBA, and Department of Physiology, Molecular and Cellular Biology, FCEyN, University of Buenos Aires, C1428EHA, Buenos Aires, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Zappala
authors.affiliation: Institute for Physiology, Molecular Biology and Neurosciences, CONICET-UBA, and Department of Physiology, Molecular and Cellular Biology, FCEyN, University of Buenos Aires, C1428EHA, Buenos Aires, Argentina. Electronic address: adepino@conicet.gov.ar.
authors.forename: Amaicha Mara
authors.initials: AM
authors.lastname: Depino
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D002452:Cell Count; D005260:Female; D018682:GABA Agents / Q000009:adverse effects*; D008425:Maternal Behavior / Q000502:physiology*; D051379:Mice; D017628:Microglia / Q000166:cytology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013216:Reflex, Startle / Q000502:physiology*; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D018682:GABA Agents; D014635:Valproic Acid
keywords: Astrocyte; Autism spectrum disorder; HDAC; Hypothalamus-pituitary-adrenal response; Microglia; Purkinje cells