Low hippocampal PI(4,5)P 2 contributes to reduced cognition in old mice as a result of loss of MARCKS

Laura Trovò, Tariq Ahmed, Zsuzsanna Callaerts-Vegh, Andrea Buzzi, Claudia Bagni, Marinee Chuah, Thierry Vandendriessche, Rudi D'Hooge, Detlef Balschun, Carlos G. Dotti

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36 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)449-455
Number of pages7
JournalNature Neuroscience
Issue number4
Publication statusPublished - Apr 2013
Externally publishedYes


ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Trovò, L., Ahmed, T., Callaerts-Vegh, Z., Buzzi, A., Bagni, C., Chuah, M., Vandendriessche, T., D'Hooge, R., Balschun, D., & Dotti, C. G. (2013). Low hippocampal PI(4,5)P 2 contributes to reduced cognition in old mice as a result of loss of MARCKS. Nature Neuroscience, 16(4), 449-455. https://doi.org/10.1038/nn.3342