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

Sci Rep. 2019 Dec 23;9(1):19616. doi: 10.1038/s41598-019-56133-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • CA3 Region, Hippocampal / metabolism*
  • CA3 Region, Hippocampal / pathology
  • Long-Term Potentiation / drug effects*
  • Mice
  • Mossy Fibers, Hippocampal / metabolism*
  • Mossy Fibers, Hippocampal / pathology
  • Spermidine / pharmacology*
  • Synaptic Transmission / drug effects*
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / pathology


  • Spermidine