Protein dynamics associated with failed and rescued learning in the Ts65Dn mouse model of Down syndrome

PloS One
Md Mahiuddin AhmedKatheleen J Gardiner

Abstract

Down syndrome (DS) is caused by an extra copy of human chromosome 21 (Hsa21). Although it is the most common genetic cause of intellectual disability (ID), there are, as yet, no effective pharmacotherapies. The Ts65Dn mouse model of DS is trisomic for orthologs of ∼55% of Hsa21 classical protein coding genes. These mice display many features relevant to those seen in DS, including deficits in learning and memory (L/M) tasks requiring a functional hippocampus. Recently, the N-methyl-D-aspartate (NMDA) receptor antagonist, memantine, was shown to rescue performance of the Ts65Dn in several L/M tasks. These studies, however, have not been accompanied by molecular analyses. In previous work, we described changes in protein expression induced in hippocampus and cortex in control mice after exposure to context fear conditioning (CFC), with and without memantine treatment. Here, we extend this analysis to Ts65Dn mice, measuring levels of 85 proteins/protein modifications, including components of MAP kinase and MTOR pathways, and subunits of NMDA receptors, in cortex and hippocampus of Ts65Dn mice after failed learning in CFC and after learning was rescued by memantine. We show that, compared with wild type littermate controls, (i) of ...Continue Reading

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Citations

Oct 27, 2015·Frontiers in Behavioral Neuroscience·Fiorenza StagniRenata Bartesaghi
Oct 11, 2017·Disease Models & Mechanisms·Yann HeraultVeronique Brault
Nov 12, 2015·Biology of Sex Differences·Aaron BlockKatheleen J Gardiner
Jun 1, 2018·Nature Communications·Abubakar AbidJames Zou
Nov 4, 2020·Nature Biomedical Engineering·Md Tauhidul Islam, Lei Xing
Jun 15, 2021·Frontiers in Neurology·Md Mahiuddin AhmedAmy Brooks-Kayal

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Methods Mentioned

BETA
pharmacotherapies
nucleotide exchange
dissections
Protein Assay

Software Mentioned

RL
SAS
FL

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