Postnatal behavioral and inflammatory alterations in female pups prenatally exposed to valproic acid
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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.
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Increased glial proliferation and altered astrocyte and microglial densities are observed in the hippocampus and cerebellum following VPA exposure.
“Increased glial proliferation [213] and altered astrocyte and microglial densities are observed in the hippocampus and cerebellum following VPA exposure [189].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [189]
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- Authors
- Kazlauskas, N., Campolongo, M., Lucchina, L., Zappala, C., & Depino, A. M.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Depino, Amaicha Mara
- ORCID
- Depino, Amaicha Mara
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2016-10
- Volume
- 72
- Pages
- 11-21
- ISSN
- 0306-4530 (ISSN-L)
- OpenAlex
- W2408968750
- Cited by
- 56
- References
- 37
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 8 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 7
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Conicet (submittedVersion, cc-by-nc-nd)
- Funders
- National Agency of Promotion of Science and Technology (PICT2013-1362)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- valproic acid, prenatal exposure, autism spectrum disorder, sex differences, female offspring, postnatal behavior, righting reflex, acoustic startle response, glial cell density, astrocytes, microglia, histone H3 acetylation, epigenetics, neuroinflammation, cerebellum, prefrontal cortex, hippocampus, maternal behavior
- MeSH terms
- Animals, Astrocytes, Behavior, Animal, Brain, Cell Count, Female, Maternal Behavior, Pregnancy, Prenatal Exposure Delayed Effects, Reflex, Startle, Valproic Acid, Microglia, GABA Agents, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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