The DOI matches its Crossref record; 110 of the 111 references it cites were found in a registry or an index.
Rearrangement of the dendritic morphology in limbic regions and altered exploratory behavior in a rat model of autism spectrum disorder
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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In the citing paper
“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 the citing paper
“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 the citing paper
“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]
Citations
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The valproic acid-induced rodent model of autism
Nicolini, C., & Fahnestock, M. L. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.04.017 · Cited by 622
Autism spectrum disorder: neuropathology and animal models
Varghese, M., Keshav, N., Jacot-Descombes, S., Warda, T., Wicinski, B., Dickstein, D. L., Harony-Nicolas, H., De Rubeis, S., Drapeau, E., Buxbaum, J. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1736-4 · Cited by 536
Luczynski, P., Whelan, S. O., O'SULLIVAN, C. T. D., Clarke, G. A., Shanahan, F., Dinan, T. G., & Cryan, J. F. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13291 · Cited by 360
Martínez‐Cerdeño, V. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22417 · Cited by 256
The basolateral amygdala γ‐aminobutyric acidergic system in health and disease
Prager, E. M., Bergstrom, H. C., Wynn, G. H., & Braga, M. F. M. (2015) · Journal of Neuroscience Research · doi:10.1002/jnr.23690 · Cited by 192
Metadata
- 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.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 241
- Pages
- 170-187
- ISSN
- 0306-4522 (ISSN-L)
- 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
- 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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