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Cited by 165Down syndrome and intellectual disability researchNeurogenesis and neuroplasticity mechanismsGenetics and Neurodevelopmental Disorders

Widespread Proliferation Impairment and Hypocellularity in the Cerebellum of Fetuses with Down Syndrome

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Guidi, Sandra, Ciani, Elisabetta, Bonasoni, Paola, Santini, Donatella, Bartesaghi, Renata·2011·Brain Pathology
DOI 10.1111/j.1750-3639.2010.00459.xPMC PMC8094247
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Abstract

Evidence in mouse models for Down syndrome (DS) and human fetuses with DS clearly shows severe neurogenesis impairment in various telencephalic regions, suggesting that this defect may underlie the cognitive abnormalities of DS. As cerebellar hypotrophy and motor disturbances are part of the clinical features of DS, the goal of our study was to establish whether these defects may be related to neurogenesis impairment during cerebellar development. We found that in fetuses with DS (17–21 weeks of gestation) the cerebellum had an immature pattern, a reduced volume and notably fewer cells (−25%/−50%) in all cerebellar layers. Immunohistochemistry for Ki‐67, a marker of cycling cells, showed impaired proliferation (−17%/−50%) of precursors from both cerebellar neurogenic regions (external granular layer and ventricular zone). No differences in apoptotic cell death were found in DS vs. control fetuses. The current study provides novel evidence that in the cerebellum of DS fetuses there is a generalized hypocellularity and that this defect is due to proliferation impairment, rather than to an increased cell death. The reduced proliferation potency found in the DS fetal cerebellum, in conjunction with previous evidence, strengthens the idea that the trisomic brain is characterized by widespread neurogenesis disruption.

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  • Analyses of fetal brain tissue indicate that there are fewer proliferating cells, as measured by expression of the cell cycle marker Ki67 and of cyclin proteins, in the germinal zones of the hippocampus and cortex in Down syndrome.

    “Analyses of fetal brain tissue indicate that there are fewer proliferating cells, as measured by their expression of the cell cycle marker Ki67 and of cyclin proteins, in the germinal zones of the hippocampus and cortex in DS40,42–44,47,50,64.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [43]

    The Results (page not supplied) report a previous finding of fewer proliferating cells in fetal Down syndrome hippocampal regions and the ventricular germinal matrix, and identify Ki-67 as a marker of proliferating cells. This paper studies the cerebellum and does not report cyclin-protein measurements in the hippocampus or cortex, so it supports only part of the attributed claim. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with Down syndrome than in controls, albeit based on small sample sizes.

    “The fetal cortex, cerebellum and hippocampus have all been shown to contain fewer neurons in individuals with DS than in controls40–48, albeit based on small sample sizes17.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [43]

  • The presence of fewer cycling cells and the reduced number of progenitors both support the suggestion that neurogenesis is reduced during development in Down syndrome, although these data do not distinguish between slower progenitor proliferation or premature progenitor cell cycle exit.

    “Together, the presence of fewer cycling cells and the reduced number of progenitors both support the suggestion that neurogenesis is reduced during development in DS, although these data do not distinguish between slower progenitor proliferation or premature progenitor cell cycle exit.”

    From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [43]

  • During 17-21 weeks gestation, fewer neurons were found in the hippocampus, cerebellum, and multiple thalamic nuclei in fetuses with Down syndrome.

    “During the same time period (17–21 weeks gestation) fewer neurons were found in the hippocampus (Guidi et al., 2008), cerebellum (Guidi et al., 2011), and multiple thalamic nuclei (Stagni et al., 2020).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Guidi et al., 2011

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Authors
Guidi, S., Ciani, E., Bonasoni, P., Santini, D., & Bartesaghi, R.
Affiliations
  • University of Bologna (IT)
  • IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2010-12-06
Volume
21
Issue
4
Pages
361-373
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/j.1750-3639.2010.00459.x
PMC
PMC8094247
OpenAlex
W1820550045
Cited by
165
References
4
Citations by year
2026: 5 · 2025: 7 · 2024: 12 · 2023: 15 · 2022: 17 · 2021: 11 · 2020: 25 · 2019: 11 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 7 · 2013: 14 · 2012: 8
FWCI
9.23
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Brain Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Down syndrome, cerebellum, fetal brain development, external granular layer, ventricular zone, Ki-67, apoptosis, cerebellar development
MeSH terms
Cerebellum, Down Syndrome, Female, Fetus, Humans, Immunohistochemistry, Male, Cell Proliferation, Neurogenesis

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