Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome

Richard J. Siarey, Angelina Kline-Burgess, Madelaine Cho, Andrea Balbo, Tyler K. Best, Chie Harashima, Eric Klann, Zygmunt Galdzicki

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1266-1277
Number of pages12
JournalJournal of Neurochemistry
Volume98
Issue number4
DOIs
StatePublished - Aug 2006

Keywords

  • AMPA receptor
  • Calcium/ calmodulin-dependent protein kinase II
  • Extracellular signal-regulated kinase
  • Long-term potentiation
  • Phosphatidylinositol 3-kinase
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome'. Together they form a unique fingerprint.

  • Cite this