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Cited by 48Down syndrome and intellectual disability researchGenetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology Research

Alterations to Dendritic Spine Morphology, but Not Dendrite Patterning, of Cortical Projection Neurons in Tc1 and Ts1Rhr Mouse Models of Down Syndrome

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Haas, Matilda A., Bell, Donald, Slender, Amy, Lana-Elola, Eva, Watson-Scales, Sheona, Fisher, Elizabeth M. C., Tybulewicz, Victor L. J., Guillemot, François·2013·PLoS ONE
DOI 10.1371/journal.pone.0078561PMC PMC3813676
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Abstract

Down Syndrome (DS) is a highly prevalent developmental disorder, affecting 1/700 births. Intellectual disability, which affects learning and memory, is present in all cases and is reflected by below average IQ. We sought to determine whether defective morphology and connectivity in neurons of the cerebral cortex may underlie the cognitive deficits that have been described in two mouse models of DS, the Tc1 and Ts1Rhr mouse lines. We utilised in utero electroporation to label a cohort of future upper layer projection neurons in the cerebral cortex of developing mouse embryos with GFP, and then examined neuronal positioning and morphology in early adulthood, which revealed no alterations in cortical layer position or morphology in either Tc1 or Ts1Rhr mouse cortex. The number of dendrites, as well as dendrite length and branching was normal in both DS models, compared with wildtype controls. The sites of projection neuron synaptic inputs, dendritic spines, were analysed in Tc1 and Ts1Rhr cortex at three weeks and three months after birth, and significant changes in spine morphology were observed in both mouse lines. Ts1Rhr mice had significantly fewer thin spines at three weeks of age. At three months of age Tc1 mice had significantly fewer mushroom spines--the morphology associated with established synaptic inputs and learning and memory. The decrease in mushroom spines was accompanied by a significant increase in the number of stubby spines. This data suggests that dendritic spine abnormalities may be a more important contributor to cognitive deficits in DS models, rather than overall neuronal architecture defects.

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  • Recent studies using complementary mouse models of DS (Ts65Dn, Ts2Cje, Tc1, Dp16) reported an activated microglia phenotype during brain development, with functional morphological alterations and elevated pro-inflammatory cytokines, accompanied by a reduction of neuronal dendritic spines.

    “Recent studies using complementary mouse models of DS, including Ts65Dn, Ts2Cje, Tc1, and Dp16 mice, reported an activated phenotype in microglia cells during brain development, as evidenced by functional morphological alterations and elevated pro-inflammatory cytokines, accompanied by a reduction of neuronal dendritic spines.26,27,28,29”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [28]

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Authors
Haas, M. A., Bell, D., Slender, A., Lana-Elola, E., Watson-Scales, S., Fisher, E. M. C., Tybulewicz, V. L. J., & Guillemot, F.
Affiliations
  • National Institute for Medical Research (GB)
  • UCL Queen Square Institute of Neurology (GB)
Corresponding author
Haas, Matilda A.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-10-30
Volume
8
Issue
10
Pages
e78561
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0078561
PMC
PMC3813676
OpenAlex
W2009865652
Cited by
48
References
1
Citations by year
2026: 1 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 6 · 2013: 1
FWCI
3.41
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (U117527252, U117570528, 098327/Z/12/Z)
  • Medical Research Council (U117570528, U117527252)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability 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
Down syndrome, dendritic spine morphology, cortical projection neurons, mushroom spines, intellectual disability, cognitive impairment, synaptic input, dendritic branching, cortical development
MeSH terms
Animals, Cerebral Cortex, Disease Models, Animal, Down Syndrome, Female, Phenotype, Dendritic Spines, Green Fluorescent Proteins, Mice

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