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

被引:143
作者
Mothet, J. P. [1 ]
Rouaud, E. [1 ]
Sinet, P. -M. [1 ]
Potier, B. [1 ]
Jouvenceau, A. [1 ]
Dutar, P. [1 ]
Videau, C. [1 ]
Epelbaum, J. [1 ]
Billard, J. -M. [1 ]
机构
[1] Univ Paris Descartes, Fac Med, UMR 549, INSERM, F-75014 Paris, France
关键词
aging; astrocyte; glutamate; hippocampus; NMDA receptor; synaptic plasticity;
D O I
10.1111/j.1474-9726.2006.00216.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:267 / 274
页数:8
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