A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory

Aging Cell. 2006 Jun;5(3):267-74. doi: 10.1111/j.1474-9726.2006.00216.x.


Age-associated deficits in learning and memory are closely correlated with impairments of synaptic plasticity. Analysis of N-methyl-D-aspartate receptor (NMDAr)-dependent long-term potentiation (LTP) in CA1 hippocampal slices indicates that the glial-derived neuromodulator D-serine is required for the induction of synaptic plasticity. During aging, the content of D-serine and the expression of its synthesizing enzyme serine racemase are significantly decreased in the hippocampus. Impaired LTP and NMDAr-mediated synaptic potentials in old rats are rescued by exogenous D-serine. These results highlight the critical role of glial cells and presumably astrocytes, through the availability of D-serine, in the deficits of synaptic mechanisms of learning and memory that occur in the course of aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Binding Sites
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Learning / physiology*
  • Long-Term Potentiation / drug effects
  • Male
  • Memory / physiology*
  • Neuroglia / metabolism*
  • Neurotransmitter Agents / biosynthesis
  • Neurotransmitter Agents / metabolism*
  • Neurotransmitter Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Serine / biosynthesis
  • Serine / metabolism*
  • Serine / pharmacology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Time Factors


  • Neurotransmitter Agents
  • Receptors, N-Methyl-D-Aspartate
  • Serine