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PLoS Biol. 2016 Sep 29;14(9):e1002563. doi: 10.1371/journal.pbio.1002563. eCollection 2016 Sep.

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release.

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Institute for Biology/Genetics, Freie Universität Berlin, Berlin, Germany.
NeuroCure, Charité, Berlin, Germany.
Georg-August-Universität Göttingen, Molecular Neurobiology of Behavior, Göttingen, Germany.
Max Planck Institute of Psychiatry, Munich, Germany.
Centre for Systems Biological Analysis, University of Freiburg, Freiburg, Germany.
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Institute for Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
BioTechMed Graz, Graz, Austria.


Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.

Conflict of interest statement

The authors have declared that no competing interests exist.

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