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Cited by 141Down syndrome and intellectual disability researchNeuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental Disorders

Excitatory-inhibitory relationship in the fascia dentata in the Ts65Dn mouse model of down syndrome.

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Belichenko, Pavel V., Kleschevnikov, Alexander M., Masliah, Eliezer, Wu, Chengbiao, Takimoto‐Kimura, Ryoko, Salehi, Ahmad, Mobley, William C.·2009·Journal of Comparative Neurology
DOI 10.1002/cne.21895PMC PMC8480942
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Abstract

Down syndrome (DS) is a neurological disorder causing impaired learning and memory. Partial trisomy 16 mice (Ts65Dn) are a genetic model for DS. Previously, we demonstrated widespread alterations of pre‐ and postsynaptic elements and physiological abnormalities in Ts65Dn mice. The average diameter of presynaptic boutons and spines in the neocortex and hippocampus was enlarged. Failed induction of long‐term potentiation (LTP) due to excessive inhibition was observed. In this paper we investigate the morphological substrate for excessive inhibition in Ts65Dn. We used electron microscopy (EM) to characterize synapses, confocal microscopy to analyze colocalization of the general marker for synaptic vesicle protein with specific protein markers for inhibitory and excitatory synapses, and densitometry to characterize the distribution of the receptor and several proteins essential for synaptic clustering of neurotransmitter receptors. EM analysis of synapses in the Ts65Dn vs. 2N showed that synaptic opposition lengths were significantly greater for symmetric synapses (∼18%), but not for asymmetric ones. Overall, a significant increase in colocalization coefficients of glutamic acid decarboxylase (GAD)65/p38 immunoreactivity (IR) (∼27%) and vesicular GABA transporter (VGAT)/p38 IR (∼41%) was found, but not in vesicular glutamate transporter 1 (VGLUT1)/p38 IR. A significant overall decrease of IR in the hippocampus of Ts65Dn mice compared with 2N mice for glutamate receptor 2 (GluR2; ∼13%) and anti‐γ‐aminobutyric acid (GABA)A receptor β2/3 subunit (∼20%) was also found. The study of proteins essential for synaptic clustering of receptors revealed a significant increase in puncta size for neuroligin 2 (∼13%) and GABA A receptor‐associated protein (GABARAP; ∼13%), but not for neuroligin 1 and gephyrin. The results demonstrate a significant alteration of inhibitory synapses in the fascia dentata of Ts65Dn mice. J. Comp. Neurol. 512:453–466, 2009. © 2008 Wiley‐Liss, Inc.

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  • A significant increase in the number of inhibitory synapses without any changes in excitatory synapses identified in Ts65Dn.

    “Finally, a significant increase in the number of inhibitory synapses without any changes in excitatory synapses identified (Belichenko et al., 2009).”

    From Neurodevelopment in Down syndrome: Concordance in humans and models (2022) · cites this paper as Belichenko et al., 2009

    The Results section, “Selective changes in the ultrastructure of symmetric synapses in the Ts65Dn FD” (page unavailable), reports no significant difference in total synapse density or in the ratio of asymmetric to symmetric synapses. It found longer symmetric synapses, not a significant increase in their number. The Discussion reports more puncta for inhibitory-synapse markers, but those puncta are not a count of synapses. (LLM, conf=0.89)

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Authors
Belichenko, P. V., Kleschevnikov, A. M., Masliah, E., Wu, C., Takimoto‐Kimura, R., Salehi, A., & Mobley, W. C.
Affiliations
  • Stanford Medicine (US)
  • University of California San Diego (US)
Corresponding author
Belichenko, Pavel V.
ORCID
Venue
Journal of Comparative Neurology
Publisher
Wiley
Published
2008-11-25
Volume
512
Issue
4
Pages
453-466
ISSN
  • 0021-9967 (ISSN-L)
  • 1096-9861
DOI
10.1002/cne.21895
PMC
PMC8480942
OpenAlex
W2068318808
Cited by
141
References
3
Citations by year
2025: 5 · 2024: 2 · 2023: 6 · 2022: 9 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 10 · 2014: 7 · 2013: 16 · 2012: 20
FWCI
11.26
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Comparative Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (R01AG016999, AG 16999)
  • National Institute of Neurological Disorders and Stroke (NS 38869, R01NS038869)
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
Down syndrome, Ts65Dn mouse model, dentate gyrus, inhibitory synapses, excitation-inhibition balance, synaptic morphology, GABAergic synapses, GAD65, vesicular GABA transporter, VGLUT1, GABAA receptor, GluR2, neuroligin-2, GABARAP, gephyrin, hippocampus
MeSH terms
Animals, Carrier Proteins, Disease Models, Animal, Down Syndrome, Female, Glutamate Decarboxylase, Humans, Male, Membrane Proteins, Nerve Tissue Proteins, Peptide Fragments, Recombinant Fusion Proteins, Synapses, Biomarkers, Cell Adhesion Molecules, Neuronal, Synaptophysin, Receptors, Glutamate, Presynaptic Terminals, Receptors, GABA, Dentate Gyrus, Neural Cell Adhesion Molecules, Dendritic Spines, Vesicular Inhibitory Amino Acid Transport Proteins, Vesicular Glutamate Transport Protein 1, Mice, Inhibitory Postsynaptic Potentials

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