Normal Protein Composition of Synapses in Ts65Dn Mice: a Mouse Model of Down Syndrome

Overview

Journal J Neurochem

Specialties Chemistry
Neurology

Date 2009 May 21

PMID 19453946

Citations 13

Authors

Fabian Fernandez

Jonathan C Trinidad

Martina Blank

Dong-Dong Feng

Alma L Burlingame

Craig C Garner

Affiliations

Soon will be listed here.

Abstract

Down syndrome (DS) is the most prevalent form of intellectual disability caused by the triplication of approximately 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.

Citing Articles

Early Chronic Fluoxetine Treatment of Ts65Dn Mice Rescues Synaptic Vesicular Deficits and Prevents Aberrant Proteomic Alterations.

Fatemi S, Otte E, Folsom T, Eschenlauer A, Roper R, Aman J Genes (Basel). 2024; 15(4).

PMID: 38674386 PMC: 11049293. DOI: 10.3390/genes15040452.

Reduced synaptic proteins and SNARE complexes in Down syndrome with Alzheimer's disease and the Dp16 mouse Down syndrome model: Impact of APP gene dose.

Chen X, Zuo X, Becker A, Head E, Mobley W Alzheimers Dement. 2022; 19(5):2095-2116.

PMID: 36370135 PMC: 10175517. DOI: 10.1002/alz.12835.

Re-establishment of the epigenetic state and rescue of kinome deregulation in Ts65Dn mice upon treatment with green tea extract and environmental enrichment.

De Toma I, Ortega M, Catuara-Solarz S, Sierra C, Sabido E, Dierssen M Sci Rep. 2020; 10(1):16023.

PMID: 32994493 PMC: 7524756. DOI: 10.1038/s41598-020-72625-z.

DYRK1A Overexpression Alters Cognition and Neural-Related Proteomic Pathways in the Hippocampus That Are Rescued by Green Tea Extract and/or Environmental Enrichment.

De Toma I, Ortega M, Aloy P, Sabido E, Dierssen M Front Mol Neurosci. 2019; 12:272.

PMID: 31803016 PMC: 6873902. DOI: 10.3389/fnmol.2019.00272.

Phosphoproteomic Alterations of Ionotropic Glutamate Receptors in the Hippocampus of the Ts65Dn Mouse Model of Down Syndrome.

Gomez de Salazar M, Grau C, Ciruela F, Altafaj X Front Mol Neurosci. 2018; 11:226.

PMID: 30140203 PMC: 6095006. DOI: 10.3389/fnmol.2018.00226.

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