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Prenatal exposure of rats to valproic acid reproduces the cerebellar anomalies associated with autism
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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“Cell density is increased in the hippocampus [94], but it is decreased in the cerebellum [164] and the superior olivary nuclei of the brainstem [221] following prenatal VPA exposure.”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [164]
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Metadata
- 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)
- 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
- 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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