D-Serine enhances impaired long-term potentiation in CA1 subfield of hippocampal slices from aged senescence-accelerated mouse prone/8

The molecular and cellular mechanisms underlying the cognitive deficiency of senescence-accelerated Mouse prone/8 (SAMP8) have been attributed to many pathological changes in neurons. Recently, increasing evidence has shown that astrocytes, by mean of D-serine, involve in the process of synaptic transmission. Here we reported that the long-term potentiation (LTP) in CA1 area of hippocampal slices prepared from 2-, 6- and 12-month-old SAMP8 significantly decreased with age. Meanwhile, the UP in the slices of 6- and 12-month-old mice markedly decreased below that of the age-matched normal strain SAMR1. Supplement with exogenous D-serine, a main product of astrocytes and a coagonist at the glycin-binding site of N-methyl-D-aspartate (NMDA) receptors, not only directly enhanced the deficient UP but also rescued the abolished UP by D-amino acid oxidase (DAAO) in slices from 12-month-old SAMP8. This ameliorative effect of D-serine was inhibited by either AP-V or 5,7-dichlorokynurenic acid (DCKA). These results suggest. that absence of D-serine or dysfunction of the astrocytes possibly was one of mechanisms underlying the decrease of NMDA receptor-dependent UP and cognition in aged SAMP8. (c) 2004 Elsevier Ireland Ltd. All rights reserved.