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Cited by 268Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

Cerebellar Purkinje Cells are Reduced in a Subpopulation of Autistic Brains: A Stereological Experiment Using Calbindin-D28k

Whitney, Elizabeth R., Kemper, Thomas L., Bauman, Margaret L., Rosene, Douglas L., Blatt, Gene J.·2008·The Cerebellum
DOI 10.1007/s12311-008-0043-y
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Abstract

Although a decreased number of cerebellar Purkinje cells (PCs) in the autistic brain has been widely reported with a variety of qualitative and quantitative methods, the more accurate method of cell counting with modern stereology has not yet been employed. An additional possible problem with prior reports is the use of Nissl staining to identify the PCs, as this can miss cells due to staining irregularities. In the present study, PCs were immunostained for calbindin-D28k (CB), as this has been shown to be a more reliable marker for PCs than the Nissl stain, with more than 99% of the PCs immunopositive (Whitney, Kemper, Rosene, Bauman, Blatt, J Neurosci Methods 168:42-47, 2008). Using stereology and CB immunostaining, the density of PCs was determined in serial sections from a consistently defined area of the cerebellar hemisphere in four control and six autistic brains, with the density of PCs then correlated with the clinical severity of autism. Overall, there was no significant difference in the density of PCs between the autistic and control groups. However, three of six autistic brains had PC numbers that fell within the control range, whereas the remaining three autistic brains revealed a reduction compared with the control brains. These data demonstrate that a reduction in cerebellar PCs was not a consistent feature of these autistic brains and that it occurred without discernible correlation between their density and the clinical features or severity of autism.

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  • Epigenetic anomalies in histone methylation patterns may contribute to the cerebellum neuroanatomical alterations, especially concerning Purkinje cells, observed in some individuals with ASD.

    “epigenetic anomalies in histone methylation patterns may contribute to the cerebellum neuroanatomical alterations, especially concerning Purkinje cells, observed in some individuals with ASD [for a review of cerebellar abnormalities reported in autism, see Ref. (184) and (185)].”

    From Gene × Environment Interactions in Autism Spectrum Disorders: Role of Epigenetic Mechanisms (2014) · cites this paper as [185]

  • Reduced Purkinje cell numbers may not be present in all autistic cases; in three of six autistic brains, Purkinje cell numbers approximated controls.

    “Whitney et al. [6] has suggested that the presence of reduced numbers of PCs in the brains of autistic individuals may not be present in all cases. In three of the six brains of autistic individuals, the number of PCs closely approximated that of the controls.”

    From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [6]

  • In postmortem brains of autistic individuals, there is a significant decrease in Purkinje cells, primarily in the posterolateral neocerebellar cortex and adjacent archicerebellar cortex of the cerebellar hemispheres, across age, sex, and cognitive ability.

    “almost all of the postmortem brains of autistic individuals studied to date, regardless of age, sex, and cognitive ability, have shown a significant decrease in the number of Purkinje cells (PC), primarily in the posterolateral neocerebellar cortex and adjacent archicerebellar cortex of the cerebellar hemispheres [4–7].”

    From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [6]

  • In autistic individuals with Purkinje cell loss, the absence of neuronal loss in the inferior olive indicates that Purkinje cell loss occurred before the inferior olive-Purkinje cell relationship is established shortly before birth.

    “In the brains of autistic individuals with loss of PCs there is no neuronal loss in the synaptically related inferior olive. This tight relationship is established shortly before birth. Once this bond is made, any loss of PCs thereafter results in an obligatory retrograde cell loss of inferior olivary neurons [6, 10, 11].”

    From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [6]

  • The most consistently reported neuropathology in autism is a reduction in cerebellar Purkinje cells.

    “The most consistently reported neuropathology is a reduction in cerebellar Purkinje cells, the sole outflow of cerebellar cortex [6, 120].”

    From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [6]

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Authors
Whitney, E. R., Kemper, T. L., Bauman, M. L., Rosene, D. L., & Blatt, G. J.
Affiliations
Boston University (US)
Corresponding author
Whitney, Elizabeth R.
ORCID
Venue
The Cerebellum
Publisher
Springer Science and Business Media LLC
Published
2008-06-28
Volume
7
Issue
3
Pages
406-416
ISSN
  • 1473-4222 (ISSN-L)
  • 1473-4230
DOI
10.1007/s12311-008-0043-y
OpenAlex
W2136932965
Cited by
268
References
47
Citations by year
2026: 9 · 2025: 11 · 2024: 9 · 2023: 12 · 2022: 12 · 2021: 12 · 2020: 19 · 2019: 14 · 2018: 15 · 2017: 14 · 2016: 27 · 2015: 20 · 2014: 16 · 2013: 27 · 2012: 15
FWCI
6.03
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • The Cerebellum (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Hussman Foundation
  • National Institutes of Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD039459, HD39459)
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
Purkinje cells, autism spectrum disorder, calbindin-D28k, stereology, cell counting, cerebellum, Nissl staining
MeSH terms
Adolescent, Adult, Autistic Disorder, Brain, Cerebellum, Female, Humans, Male, Middle Aged, Purkinje Cells, Reference Values, Severity of Illness Index, Biomarkers, Young Adult, Calbindins, S100 Calcium Binding Protein G, Calbindin 1

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