Cited by 381Autism Spectrum Disorder ResearchPharmacological Effects and Toxicity StudiesGenetics and Neurodevelopmental Disorders

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Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism

Ingram, Jennifer L, Peckham, Stacey M, Tisdale, Barbara, Rodier, Patricia M·2000·Neurotoxicology and Teratology

DOI 10.1016/s0892-0362(99)00083-5

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Abstract

Abnormalities in anatomy and function of the cranial nerve motor nuclei have been demonstrated in some people with autism and can be modeled in rats by exposure to valproic acid during neural tube closure. Reductions in Purkinje cell number and cerebellar volume, particularly of the posterior lobe, have also been reported in people with autism. Thus, a stereological examination of cerebellar morphology was undertaken in valproate-exposed rats. Compared to controls, rats exposed to a single dose of 600-mg/kg sodium valproate on embryonic day 12.5 had significantly fewer Purkinje cells in the cerebellar vermis and a reduction short of significant in the hemispheres. The diminished cell numbers reflect reductions in tissue volume throughout the cerebellum, rather than cell density, which was unaffected in all regions. Within the vermis, the reduction in volume was significantly greater in the posterior lobe than in the anterior lobe. The results parallel those reported for human cases of autism.

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Self-citation
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Authors: Ingram, J. L., Peckham, S. M., Tisdale, B., & Rodier, P. M.
Affiliations: University of Rochester Medicine (US)
Corresponding author: Rodier, Patricia M
ORCID: Ingram, Jennifer L
Venue: Neurotoxicology and Teratology
Publisher: Elsevier BV
Published: 2000-05
Volume: 22
Issue: 3
Pages: 319-324
ISSN: 0892-0362 (ISSN-L)
DOI: 10.1016/s0892-0362(99)00083-5
OpenAlex: W2069106140
Cited by: 381
References: 23
Citations by year: 2026: 7 · 2025: 10 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 19 · 2020: 17 · 2019: 10 · 2018: 15 · 2017: 18 · 2016: 27 · 2015: 23 · 2014: 27 · 2013: 24 · 2012: 25
FWCI: 2.65
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neurotoxicology and Teratology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01hd034295-05)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01 HD 35466, R01 HD 34295, P01HD035466)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords: valproic acid, prenatal exposure, autism spectrum disorder, cerebellum, Purkinje cells, cerebellar vermis, cerebellar volume, neural tube closure, stereology, animal models of autism, cranial nerve motor nuclei
MeSH terms: Animals, Anticonvulsants, Autistic Disorder, Behavior, Animal, Cell Count, Cerebellar Diseases, Female, Pregnancy, Purkinje Cells, Valproic Acid, Rats, Long-Evans, Rats

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Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism

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