期刊
NATURE NEUROSCIENCE
卷 16, 期 4, 页码 449-U114出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.3342
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资金
- Fund for Scientific Research Flanders (FWO)
- Federal Office for Scientific Affairs [IUAP P6/43]
- Flemish Government
- Belgian Government [IAP 7/16]
- Spanish Ministry of Science and Innovation [CSD2010-00064, SAF2010-14906]
- Katholieke University of Leuven
- K.U. Leuven GOA [12/008]
Cognitive and motor performances decline during aging. Although it is clear that such signs reflect synaptic compromise, the underlying mechanisms have not been defined. We found that the levels and activity of the synaptic plasticity modulators phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P-2) and phospholipase C gamma (PLC gamma) were substantially reduced in hippocampal synaptic membranes from old mice. In addition, these membranes contained reduced levels of the PI(4,5)P-2-clustering molecule myristoylated alanine-rich C kinase substrate (MARCKS). Consistent with a cause-effect relationship, raising MARCKS levels in the brain of old mice led to increased synaptic membrane clustering of PI(4,5)P-2 and to PLC gamma activation. MARCKS overexpression in the hippocampus of old mice or intraventricular perfusion of MARCKS peptide resulted in enhanced long-term potentiation and improved memory. These results reveal one of the mechanisms involved in brain dysfunction during aging.
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