PLoS Biology (Sep 2016)

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

  • Varun K Gupta,
  • Ulrike Pech,
  • Anuradha Bhukel,
  • Andreas Fulterer,
  • Anatoli Ender,
  • Stephan F Mauermann,
  • Till F M Andlauer,
  • Emmanuel Antwi-Adjei,
  • Christine Beuschel,
  • Kerstin Thriene,
  • Marta Maglione,
  • Christine Quentin,
  • René Bushow,
  • Martin Schwärzel,
  • Thorsten Mielke,
  • Frank Madeo,
  • Joern Dengjel,
  • André Fiala,
  • Stephan J Sigrist

DOI
https://doi.org/10.1371/journal.pbio.1002563
Journal volume & issue
Vol. 14, no. 9
p. e1002563

Abstract

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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.