Spermidine protects from age-related synaptic alterations at hippocampal mossy fiber-CA3 synapses


  • M. Maglione
  • G. Kochlamazashvili
  • T. Eisenberg
  • B. Rácz
  • E. Michael
  • D. Toppe
  • A. Stumpf
  • A. Wirth
  • A. Zeug
  • F.E. Müller
  • L. Moreno-Velasquez
  • R.P. Sammons
  • S.J. Hofer
  • F. Madeo
  • T. Maritzen
  • N. Maier
  • E. Ponimaskin
  • D. Schmitz
  • V. Haucke
  • S.J. Sigrist


  • Scientific Reports


  • Sci Rep 9 (1): 19616


  • Aging is associated with functional alterations of synapses thought to contribute to age-dependent memory impairment (AMI). While therapeutic avenues to protect from AMI are largely elusive, supplementation of spermidine, a polyamine normally declining with age, has been shown to restore defective proteostasis and to protect from AMI in Drosophila. Here we demonstrate that dietary spermidine protects from age-related synaptic alterations at hippocampal mossy fiber (MF)-CA3 synapses and prevents the aging-induced loss of neuronal mitochondria. Dietary spermidine rescued age-dependent decreases in synaptic vesicle density and largely restored defective presynaptic MF-CA3 long-term potentiation (LTP) at MF-CA3 synapses (MF-CA3) in aged animals. In contrast, spermidine failed to protect CA3-CA1 hippocampal synapses characterized by postsynaptic LTP from age-related changes in function and morphology. Our data demonstrate that dietary spermidine attenuates age-associated deterioration of MF-CA3 synaptic transmission and plasticity. These findings provide a physiological and molecular basis for the future therapeutic usage of spermidine.