Synaptic structural abnormalities in the Ts65Dn mouse model of down syndrome
Abstract
The Ts65Dn mouse is a genetic model for Down syndrome. Although this mouse shows abnormalities in cognitive function that implicate hippocampus as well as marked deficits in hippocampal long-term potentiation, the structure of the hippocampus has been little studied. We characterized synaptic structure in Ts65Dn and control (2N) mice, studying the hippocampus (fascia dentata, CA1) as well as the motor and somatosensory cortex, entorhinal cortex, and medial septum. Confocal microscopy was used to examine immunostained presynaptic boutons and to detail the structure of dendrites after Lucifer yellow microinjection. Both presynaptic and postsynaptic elements were significantly enlarged in Ts65Dn in all regions examined. The changes were detected at the youngest age examined (postnatal day 21) and in adults. In studies detailing the changes in fascia dentata and motor cortex, the enlargement of spines affected the entire population, resulting in the presence of spines whose volume was greatly increased. Electron microscopy confirmed that boutons and spines were enlarged and demonstrated abnormalities in the internal membranes of both. In addition, spine density was decreased on the dendrites of dentate granule cells, and there was reorganization of inhibitory inputs, with a relative decrease in inputs to dendrite shafts and an increase in inputs to the necks of spines. Taken together, the findings document widespread abnormalities of synaptic structure that recapitulate important…
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Ts65Dn mice exhibit deficient neurological structural phenotypes in brain regions where the current study found DYRK1A overexpression, including during perinatal or early postnatal ages.
“Ts65Dn mice do exhibit deficient neurological structural phenotypes in brain regions where we found DYRK1A overexpression including during perinatal or early postnatal ages (Baxter et al., 2000; Belichenko et al., 2004; Bianchi et al., 2010; Chakrabarti et al., 2007; Roper et al., 2006b; Stagni et al., 2016).”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Belichenko et al., 2004
The length of symmetric synapses appears to be significantly longer in the Ts65Dn hippocampus indicating an alteration of structure of typically inhibitory connections.
“Additionally, the length of symmetric synapses appears to be significantly longer in the Ts65Dn hippocampus indicating an alteration of structure of typically inhibitory connections.”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Belichenko et al., 2004
Though Ts65Dn fails to capture the majority of the volumetric changes observed in humans, they do appear to recapitulate the synaptic changes as decreases in synaptic density have been identified in both the hippocampus and the neocortex.
“Though Ts65Dn fails to capture the majority of the volumetric changes observed in humans, they do appear to recapitulate the synaptic changes as decreases in synaptic density have been identified in both the hippocampus and the neocortex (Belichenko et al., 2004; Chakrabarti et al., 2007).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Belichenko et al., 2004
Close examination has found that both pre-synaptic boutons and spines are enlarged and the physical distribution of afferent inputs is changed compared to their euploid controls in Ts65Dn.
“Close examination has found that both pre-synaptic boutons and spines are enlarged and the physical distribution of afferent inputs is changed compared to their euploid controls (Belichenko et al., 2004).”
From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Belichenko et al., 2004
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References 80 · Cited by 297
- Authors
- Belichenko, P. V., Masliah, E., Kleschevnikov, A. M., Villar, A. J., Epstein, C. J., Salehi, A., & Mobley, W. C.
- Affiliations
- Stanford Medicine (US)
- University of California San Diego (US)
- University of California, San Francisco (US)
- Corresponding author
- Belichenko, Pavel V.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 2004-10-28
- Volume
- 480
- Issue
- 3
- Pages
- 281-298
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W1996154142
- Cited by
- 297
- References
- 80
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 2 · 2023: 10 · 2022: 14 · 2021: 11 · 2020: 9 · 2019: 7 · 2018: 13 · 2017: 14 · 2016: 11 · 2015: 15 · 2014: 17 · 2013: 16 · 2012: 21
- FWCI
- 15.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hd031498-05)
- National Institute on Aging (R01AG016999, AG 16999)
- National Institute of Neurological Disorders and Stroke (NS 38869, R01NS038869)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-31498)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Ts65Dn mouse model, Down syndrome, synaptic structure, dendritic spines, presynaptic terminals, hippocampus, dentate gyrus, CA1, motor cortex, somatosensory cortex, entorhinal cortex, medial septum, dendritic spine density, long-term potentiation
- MeSH terms
- Animals, Brain, Disease Models, Animal, Down Syndrome, Female, Hippocampus, Male, Mice, Inbred C57BL, Mice, Neurologic Mutants, Motor Cortex, Reference Values, Somatosensory Cortex, Synapses, Presynaptic Terminals, Dendritic Spines, Mice
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