Reversal of aging-associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function.
Deficits in learning and memory accompanied by age-related neurodegenerative diseases are closely related to the impairment of synaptic plasticity. In this study, we investigated the role of thiol redox status in the modulation of the N-methyl-d-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) in CA1 areas of hippocampal slices. Our results demonstrated that the impaired LTP induced by aging could be reversed by acute administration of reductants that can regulate thiol redox status directly, such as dithiothreitol or β-mercaptoethanol, but not by classical anti-oxidants such as vitamin C or trolox. This repair was mediated by the recruitment of aging-related deficits in NMDAR function induced by these reductants and was mimicked by glutathione, which can restore the age-associated alterations in endogenous thiol redox status. Moreover, antioxidant prevented but failed to reverse H(2)O(2) -induced impairment of NMDAR-mediated synaptic plasticity. These results indicate that the restoring of thiol redox status may be a more effective strategy than the scavenging of oxidants in the treatment of pre-existing oxidative injury in learning and memory.
Yang
Yuan-Jian
YJ
Department of Pharmacology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Wu
Peng-Fei
PF
Long
Li-Hong
LH
Yu
Dan-Fang
DF
Wu
Wen-Ning
WN
Hu
Zhuang-Li
ZL
Fu
Hui
H
Xie
Na
N
Jin
You
Y
Ni
Lan
L
Wang
Jian-Zhi
JZ
Wang
Fang
F
Chen
Jian-Guo
JG
D000375:Aging; D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008623:Mercaptoethanol / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D013438:Sulfhydryl Compounds; D008623:Mercaptoethanol; D004229:Dithiothreitol