The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
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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GUNDERSEN, H. J. G., BENDTSEN, T. F., KORBO, L., MARCUSSEN, N., MØLLER, A., NIELSEN, K., NYENGAARD, J. R., PAKKENBERG, B., SØRENSEN, F. B., VESTERBY, A., et al. (1988) · APMIS · doi:10.1111/j.1699-0463.1988.tb05320.x · Cited by 2,929
Autism as a strongly genetic disorder: evidence from a British twin study
Bailey, A., Le Couteur, A., Gottesman, I., Bolton, P., Simonoff, E., Yuzda, E., & Rutter, M. (1995) · Psychological Medicine · doi:10.1017/s0033291700028099 · Cited by 2,461
A clinicopathological study of autism
Bailey, A. (1998) · Brain · doi:10.1093/brain/121.5.889 · Cited by 1,083
Histoanatomic observations of the brain in early infantile autism
Bauman, M., & Kemper, T. L. (1985) · Neurology · doi:10.1212/wnl.35.6.866 · Cited by 964
New stereological methods for counting neurons
West, M. J. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90112-o · Cited by 940
Bayer, S. A., Altman, J., Russo, R. J., & Zhang, X. (1993) · PubMed · Cited by 912
(1986) · American Journal of Psychiatry · doi:10.1176/ajp.143.7.862 · Cited by 590
AUTISM IN THALIDOMIDE EMBRYOPATHY: A POPULATION STUDY
Strömland, K., Nordin, V., Miller, M. T., Åkerström, B., & Gillberg, C. (1994) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1994.tb11856.x · Cited by 453
Development of the brainstem and cerebellum in autistic patients
Hashimoto, T., Tayama, M., Murakawa, K., Yoshimoto, T., Miyazaki, M., Harada, M., & Kuroda, Y. (1995) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02178163 · Cited by 381
Fetal Valproate Syndrome: Clinical and Neuro‐developmental Features in Two Sibling Pairs
Christianson, A. L., Chester, N., & Kromberg, J. G. R. (1994) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1994.tb11858.x · Cited by 337
Courchesne, E., Townsend, J., & Saitoh, O. (1994) · Neurology · doi:10.1212/wnl.44.2.214 · Cited by 286
A male with fetal valproate syndrome and autism
Williams, P. G., & Hersh, J. H. (1997) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1997.tb07500.x · Cited by 182
The development of the purkinje cells and of the cortical layers in the cerebellum of the albino rat
Addison, W. H. F. (1911) · The Journal of Comparative Neurology · doi:10.1002/cne.900210503 · Cited by 169
Clayton‐Smith, J., & Donnai, D. (1995) · Journal of Medical Genetics · doi:10.1136/jmg.32.9.724 · Cited by 165
Autism in Fetal Alcohol Syndrome: A Report of Six Cases
Nanson, J. L. (1992) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1992.tb01417.x · Cited by 152
Korbo, L., Andersen, B. B., Ladefoged, O., & Møller, A. (1993) · Brain Research · doi:10.1016/0006-8993(93)90881-m · Cited by 147
Evaluation of valproic acid (VPA) developmental toxicity and pharmacokinetics in Sprague-Dawley rats
Binkerd, P. E. (1988) · Fundamental and Applied Toxicology · doi:10.1016/0272-0590(88)90112-1 · Cited by 140
Cerebellar Structure in Autism
Gaffney, G. (1987) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1987.04460120096044 · Cited by 131
Renowden, S. A., & Squier, M. V. (1994) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1994.tb11857.x · Cited by 42
Time of Origin of the Neurons in the Caudal Brain Stem of Rat
Nornes, H. O., & Morita, M. (2007) · Developmental Neuroscience · doi:10.1159/000112444 · Cited by 40
Olivocerebellar lesions in infants born prematurely
Takashima, S. (1982) · Brain and Development · doi:10.1016/s0387-7604(82)80020-x · Cited by 25
Rodier (1996) · doi:10.1002/(sici)1096-9861(19960624)370:2
Self-citationBurger (1998) · doi:10.1002/(sici)1098-2779(1998)4:2
Research works printed but not linked: 1
- J.L.Ingram, 1996, Valproic acid treatment in rats reproduces the cerebellar anomalies associated with autism, Teratology, 53, 86
Cited by
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The Epidemiology of Autism Spectrum Disorders
Newschaffer, C. J., Croen, L. A., Daniels, J., Giarelli, E., Grether, J. K., Levy, S. E., Mandell, D. S., Miller, L. A., Pinto-Martin, J., Reaven, J., et al. (2007) · Annual Review of Public Health · doi:10.1146/annurev.publhealth.28.021406.144007 · Cited by 1,228
Behavioral Alterations in Rats Prenatally Exposed to Valproic Acid: Animal Model of Autism
Schneider, T., & Przewłocki, R. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300518 · Cited by 959
Zoghbi, H. Y., & Bear, M. F. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009886 · Cited by 797
Malkova, N. V., Yu, C. Z., Hsiao, E. Y., Moore, M. J., & Patterson, P. H. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.01.011 · Cited by 662
Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?
Bourassa, M. W., Alim, I., Bultman, S. J., & Ratan, R. R. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.02.009 · Cited by 667
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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