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 LTP 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 LTP but also rescued the abolished LTP 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 LTP and cognition in aged SAMP8.
Yang
Sheng
S
Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
Qiao
Haifa
H
Wen
Lei
L
Zhou
Wenxia
W
Zhang
Yongxiang
Y
D000367:Age Factors; D000375:Aging / Q000235:genetics*; D000704:Analysis of Variance; D000818:Animals; D003605:D-Amino-Acid Oxidase / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000528:radiation effects; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008818:Mice, Neurologic Mutants; D012694:Serine / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
D018691:Excitatory Amino Acid Antagonists; D012694:Serine; C056639:2-amino-5-phosphopentanoic acid; C485958:Dao1 protein, mouse; D003605:D-Amino-Acid Oxidase; D007736:Kynurenic Acid; D014633:Valine; C066192:5,7-dichlorokynurenic acid