Title: Low hippocampal PI(4,5)P(2) contributes to reduced cognition in old mice as a result of loss of MARCKS
Authors: Trovo, Laura ×
Ahmed, Tariq
Callaerts-Vegh, Zsuzsanna
Buzzi, Andrea
Bagni, Claudia
Chuah, Marinee
Vandendriessche, Thierry
D'Hooge, Rudi
Balschun, Detlef
Dotti, Carlos #
Issue Date: Apr-2013
Publisher: Nature America Inc.
Series Title: Nature Neuroscience vol:16 issue:4 pages:449-U114
Article number: 10.1038/nn.3342
Abstract: 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 Cγ (PLCγ) 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 PLCγ 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.
ISSN: 1097-6256
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
Laboratory of Neuronal Differentiation (VIB-KU Leuven Center for Brain & Disease Research)
Molecular and Vascular Biology
Department of Human Genetics - miscellaneous
Formerly Thomas More Antwerpen
× corresponding author
# (joint) last author

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