Cited by 114Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

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Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder

Bringas, M.E., Carvajal-Flores, F.N., López-Ramírez, T.A., Atzori, M., Flores, G.·2013·Neuroscience

DOI 10.1016/j.neuroscience.2013.03.030

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Abstract

Valproic acid (VPA) is a blocker of histone deacetylase widely used to treat epilepsy, bipolar disorders, and migraine; its administration during pregnancy increases the risk of autism spectrum disorder (ASD) in the child. Thus, prenatal VPA exposure has emerged as a rodent model of ASD. In the present study, we aimed to investigate the effect of prenatal administration of VPA (500mg/kg) at E12.5 on the exploratory behavior and locomotor activity in a novel environment, as well as on neuronal morphological rearrangement in the prefrontal cortex (PFC), in the hippocampus, in the nucleus accumbens (NAcc), and in the basolateral amygdala (BLA) at three different ages: immediately after weaning (postnatal day 21 [PD21]), prepubertal (PD35) and postpubertal (PD70) ages. Hyper-locomotion was observed in a novel environment in VPA animals at PD21 and PD70. Interestingly, exploratory behavior assessed by the hole board test at PD70 showed a reduced frequency but an increase in the duration of head-dippings in VPA-animals compared to vehicle-treated animals. In addition, the latency to the first head-dip was longer in prenatal VPA-treated animals at PD70. Quantitative morphological analysis of dendritic spine density revealed a reduced number of spines at PD70 in the PFC, dorsal hippocampus and BLA, with an increase in the dendritic spine density in NAcc and ventral hippocampus, in prenatal VPA-treated rats. In addition, at PD70 increases in neuronal arborization were observed in the NAcc, layer 3 of the PFC, and BLA, with retracted neuronal arborization in the ventral and dorsal hippocampus. Our results extend the list of altered behaviors (exploratory behavior) detected in this model of ASD, and indicate that the VPA behavioral phenotype is accompanied by previously undescribed morphological rearrangement in limbic regions.

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See all 114

Authors: Bringas, M. E., Carvajal-Flores, F. N., López-Ramírez, T. A., Atzori, M., & Flores, G.
Affiliations: Universidad de las Américas Puebla (MX)
The University of Texas at Dallas (US)
Corresponding author: Flores, G.
ORCID: Bringas, M.E.
Atzori, M.
Flores, G.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2013-06
Volume: 241
Pages: 170-187
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2013.03.030
OpenAlex: W2033856668
Cited by: 114
References: 111
Citations by year: 2026: 7 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 4 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 8 · 2014: 4 · 2013: 5
FWCI: 5.10
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: autism spectrum disorder, valproic acid, prenatal drug exposure, limbic system, dendritic spine density, dendritic morphology, exploratory behavior, prefrontal cortex, hippocampus, nucleus accumbens, basolateral amygdala, neuronal arborization, histone deacetylase inhibition, rat model
MeSH terms: Animals, Child Development Disorders, Pervasive, Dendrites, Disease Models, Animal, Exploratory Behavior, Female, Limbic System, Pregnancy, Prenatal Exposure Delayed Effects, Valproic Acid, Rats, Sprague-Dawley, Rats, Histone Deacetylase Inhibitors

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Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder

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