title: D-serine relieves chronic lead exposure-impaired long-term potentiation in the CA1 region of the rat hippocampus in vitro.
abstract: 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 microM 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-ClKY), 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 Pb(2+)-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.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Wang
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D002908:Chronic Disease / Q000628:therapy; D004781:Environmental Exposure; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007854:Lead / Q000037:antagonists & inhibitors* / Q000633:toxicity; D020263:Lead Poisoning, Nervous System / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012694:Serine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D007854:Lead; D012694:Serine; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid