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

Mothet, J P; Rouaud, E; Sinet, P-M; Potier, B; Jouvenceau, A; Dutar, P; Videau, C; Epelbaum, J et al. · Aging Cell · 2006

basic_science · Level V

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Abstract

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.

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