Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome
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.
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The subiculum is a major output region of the hippocampus and receives input from the entorhinal cortex via the perforant pathway.
“The subiculum (SC) is a major output region of the hippocampus and receives input from the entorhinal cortex via the perforant pathway. 43”
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- Authors
- Siarey, R. J., Kline‐Burgess, A., Cho, M., Balbo, A., Best, T. K., Harashima, C., Klann, E., & Galdzicki, Z.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Baylor College of Medicine (US)
- Corresponding author
- Galdzicki, Zygmunt
- ORCID
- Klann, Eric
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2006-07-05
- Volume
- 98
- Issue
- 4
- Pages
- 1266-1277
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2003714676
- Cited by
- 86
- References
- 9
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 4 · 2013: 4 · 2012: 9
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD038417, HD38417)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Down syndrome, Ts65Dn mouse model, hippocampal synaptic plasticity, CaMKII, PI3K/Akt signaling, ERK, protein kinase A, protein kinase C, long-term potentiation, GluR1, glutamate receptor subunits, signaling pathways
- MeSH terms
- Cyclic AMP, Animals, Down Syndrome, Electric Stimulation, Electrophysiology, Hippocampus, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Neuronal Plasticity, Protein Kinase C, Blotting, Western, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Cyclic AMP-Dependent Protein Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Receptors, AMPA, Excitatory Postsynaptic Potentials, Phosphatidylinositol 3-Kinases, Receptor Cross-Talk, Mitogen-Activated Protein Kinases, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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