Normal protein composition of synapses in Ts65Dn mice: A mouse model of Down syndrome

Fabian Fernandez, Jonathan C. Trinidad, Martina Blank, Dong Dong Feng, Alma L. Burlingame, Craig C. Garner

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Down syndrome (DS) is the most prevalent form of intellectual disability caused by the triplication of ∼230 genes on chromosome 21. Recent data in Ts65Dn mice, the foremost mouse model of DS, strongly suggest that cognitive impairment in individuals with DS is a consequence of reduced synaptic plasticity because of chronic over-inhibition. It remains unclear however whether changes in plasticity are tied to global molecular changes at synapses, or are due to regional changes in the functional properties of synaptic circuits. One interesting framework for evaluating the activity state of the DS brain comes from in vitro studies showing that chronic pharmacological silencing of neuronal excitability orchestrates stereotyped changes in the protein composition of synaptic junctions. In the present study, we use proteomic strategies to evaluate whether synapses from the Ts65Dn cerebrum carry signatures characteristic of inactive cortical neurons. Our data reveal that synaptic junctions do not exhibit overt alterations in protein composition. Only modest changes in the levels of synaptic proteins and in their phosphorylation are observed. This suggests that subtle changes in the functional properties of specific synaptic circuits rather than large-scale homeostatic shifts in the expression of synaptic molecules contribute to cognitive impairment in people with DS.

Original languageEnglish (US)
Pages (from-to)157-169
Number of pages13
JournalJournal of neurochemistry
Volume110
Issue number1
DOIs
StatePublished - Jul 2009
Externally publishedYes

Keywords

  • Down syndrome
  • Mass spectrometry
  • Plasticity
  • Post-synaptic density
  • Synapse
  • Ts65Dn

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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