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Cited by 21Down syndrome and intellectual disability researchNeurogenesis and neuroplasticity mechanismsGenetics and Neurodevelopmental Disorders

Subicular hypotrophy in fetuses with Down syndrome and in the Ts65Dn model of Down syndrome

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Stagni, Fiorenza, Giacomini, Andrea, Emili, Marco, Uguagliati, Beatrice, Bonasoni, Maria Paola, Bartesaghi, Renata, Guidi, Sandra·2019·Brain Pathology
DOI 10.1111/bpa.12663PMC PMC8028278
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Abstract

Intellectual disability in Down syndrome (DS) has been attributed to neurogenesis impairment during fetal brain development. Consistently with explicit memory alterations observed in children with DS, fetuses with DS exhibit neurogenesis impairment in the hippocampus, a key region involved in memory formation and consolidation. Recent evidence suggests that the subiculum plays a unique role in memory retrieval, a process that is also altered in DS. While much attention has been devoted to the hippocampus, there is a striking lack of information regarding the subiculum of individuals with DS and DS models. In order to fill this gap, in the current study, we examined the subiculum of fetuses with DS and of the Ts65Dn mouse model of DS. We found that in fetuses with DS (gestational week: 17–21), the subiculum had a reduced thickness, a reduced cell density, a reduced density of progenitor cells in the ventricular zone, a reduced percentage of neurons, and an increased percentage of astrocytes and of cells immunopositive for calretinin—a protein expressed by inhibitory interneurons. Similarly to fetuses with DS, the subiculum of neonate Ts65Dn mice was reduced in size, had a reduced number of neurons and a reduced number of proliferating cells. Results suggest that the developmental defects in the subiculum of fetuses with DS may underlie impairment in recall memory and possibly other functions played by the subiculum. The finding that the subiculum of the Ts65Dn mouse exhibits neuroanatomical defects resembling those seen in fetuses with DS further validates the use of this model for preclinical studies.

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  • 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 [47]

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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 [47]

    The Results report 55% fewer Ki-67-positive cells in the ventricular zone overlying the subiculum of fetuses with Down syndrome than in euploid fetuses, and note a prior Ki-67 finding in the hippocampal ventricular zone. This paper does not report cyclin-protein measurements or a corresponding analysis of cortical germinal zones, so those parts of the claim are not supported by it. (LLM, conf=0.88)

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  • 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 [47]

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Authors
Stagni, F., Giacomini, A., Emili, M., Uguagliati, B., Bonasoni, M. P., Bartesaghi, R., & Guidi, S.
Affiliations
  • University of Bologna (IT)
  • Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
Corresponding author
Bartesaghi, Renata
ORCID
Venue
Brain Pathology
Publisher
Wiley
Published
2018-11-15
Volume
29
Issue
3
Pages
366-379
ISSN
  • 1015-6305 (ISSN-L)
  • 1750-3639
DOI
10.1111/bpa.12663
PMC
PMC8028278
OpenAlex
W2897080667
Cited by
21
References
5
Citations by year
2026: 3 · 2025: 4 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 1
FWCI
0.95
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)
Funders
Fondazione del Monte di Bologna e Ravenna
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, subiculum, Ts65Dn mouse model, fetal brain development, hippocampus, memory retrieval, intellectual disability, inhibitory interneurons, astrocytes
MeSH terms
Animals, Animals, Newborn, Brain, Cognition, Disease Models, Animal, Down Syndrome, Female, Fetus, Hippocampus, Humans, Male, Memory, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Mice, Neurogenesis

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