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Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome
Author(s) -
Siarey Richard J.,
KlineBurgess Angelina,
Cho Madelaine,
Balbo Andrea,
Best Tyler K.,
Harashima Chie,
Klann Eric,
Galdzicki Zygmunt
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03971.x
Subject(s) - synaptic plasticity , long term potentiation , microbiology and biotechnology , biology , protein kinase b , protein kinase c , signal transduction , synaptic fatigue , neuroscience , chemistry , receptor , biochemistry
The Ts65Dn mouse model of Down syndrome (DS) has an extra segment of chromosome (Chr.) 16 exhibits abnormal behavior, synaptic plasticity and altered function of several signaling molecules. We have further investigated signaling pathways that may be responsible for the impaired hippocampal plasticity in the Ts65Dn mouse. Here we report that calcium/calmodulin‐dependent protein kinase II (CaMKII), phosphatidylinositol 3‐kinase (PI3K)/Akt, extracellular signal‐regulated kinase (ERK), protein kinase A (PKA) and protein kinase C (PKC), all of which have been shown to be involved in synaptic plasticity, are altered in the Ts65Dn hippocampus. We found that the phosphorylation of CaMKII and protein kinase Akt was increased, whereas ERK was decreased. Activities of PKA and PKC were decreased. Furthermore, abnormal PKC activity and an absence of the increase in Akt phosphorylation were demonstrated in the Ts65Dn hippocampus after high‐frequency stimulation that induces long‐term potentiation. Our findings suggest that abnormal synaptic plasticity in the Ts65Dn hippocampus is the result of compensatory alterations involving the glutamate receptor subunit GluR1 in either one or more of these signaling cascades caused by the expression of genes located on the extra segment of Chr. 16.