D-serine relieves chronic lead exposure-impaired long-term potentiation in the CA1 region of the rat hippocampus in vitro

作者：Sun Hao; Wang Hui Li; Wang Shu^*

来源：Neuroscience Letters, 2007, 417(2): 118-122.

DOI：10.1016/j.neulet.2007.01.085

• chronic lead exposure
• glia-derived D-serine
• NMDARs
• hippocampus
• long-term potentiation

Chronic lead-exposure produces long-lasting astroglial morphological and functional changes, which disturb the neuronal functions in the hippocampus. It has been shown that glia-derived D-serine is an essential signal for N-methyl-D-aspartate receptor (NMDAR)-dependent synaptic plasticity in the hippocampal CA1 region. However, the relationship between D-serine and the chronic lead exposure-induced deficit of synaptic plasticity is not clear. In the present study, the properties Of D-serine on the chronic lead exposure-impaired synaptic plasticity in the rat hippocampal CA1 region were investigated with electrophysiological recording techniques in vitro. We found that 50 mu M D-serine rescued the chronic lead exposure-induced deficit of long-term potentiation (LTP). However, this effect could be abolished by 7-chlorokynurenic acid (7-CIKY), which is a specific antagonist of the glycine-binding site of NMDARs. In contrast, D-serine had no effect on the NMDAR-independent LTP, which was induced in the mossy-CA3 synapses. In addition, we found that D-serine rescued the acute Pb2+-impaired NMDAR-mediated excitatory postsynaptic currents (EPSCs) partially. These findings demonstrate that D-serine relieves the chronic lead exposure-induced deficit of synaptic plasticity via NMDAR activation suggesting that administration Of D-serine may be a potential therapeutic intervention to treat chronic lead exposure-impaired cognitive functions or affective disorders.

• 出版日期2007-5-1