A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory |
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| Authors: | Mothet J P Rouaud E Sinet P-M Potier B Jouvenceau A Dutar P Videau C Epelbaum J Billard J-M |
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| Affiliation: | Neurobiologie de la Croissance et de la Sénescence, UMR 549 INSERM, Faculté de Médecine, Université Paris-Descartes, 2 ter rue d'Alésia, 75014 Paris, France. |
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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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| Keywords: | aging astrocyte glutamate hippocampus NMDA receptor synaptic plasticity |
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