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

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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  • Neuropathology in prenatal VPA models depends on the dose of VPA or the age at which neuropathology was assessed.

    “Neuropathology in prenatal VPA models depends on the dose of VPA or the age at which neuropathology was assessed [42].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [42]

  • In rodent models of prenatal VPA exposure, basal dendrites show no change in length on layer II pyramidal neurons in the motor cortex, decreased length and complexity in the medial PFC and hippocampal CA1, and increased length and complexity in the nucleus accumbens and basolateral amygdala.

    “Basal dendrites in rodent models of prenatal VPA exposure show no change in length on layer II pyramidal neurons in the motor cortex [331], decreased length and complexity in the medial PFC [297] and the hippocampal CA1, and increased length and complexity in the nucleus accumbens and basolateral amygdala [42].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [42]

  • In prenatal VPA models, spine density is reduced in the PFC, orbital PFC, cerebellum, and dorsal hippocampus, but increased in the ventral hippocampus, basolateral amygdala, and nucleus accumbens.

    “Spine density is reduced in the PFC [42, 250, 297], orbital PFC [250, 297], cerebellum [250], and in the dorsal hippocampus [42, 346], but increased in the ventral hippocampus, basolateral amygdala and nucleus accumbens [42].”

    From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [42]

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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
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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