Reversal of aging-associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function
Yuan-Jian Yang
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
These authors contributed equally to this work.
Search for more papers by this authorPeng-Fei Wu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
These authors contributed equally to this work.
Search for more papers by this authorLi-Hong Long
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorDan-Fang Yu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorWen-Ning Wu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorZhuang-Li Hu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorHui Fu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorNa Xie
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorYou Jin
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorLan Ni
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorJian-Zhi Wang
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Search for more papers by this authorFang Wang
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorJian-Guo Chen
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorYuan-Jian Yang
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
These authors contributed equally to this work.
Search for more papers by this authorPeng-Fei Wu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
These authors contributed equally to this work.
Search for more papers by this authorLi-Hong Long
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorDan-Fang Yu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorWen-Ning Wu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorZhuang-Li Hu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorHui Fu
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorNa Xie
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorYou Jin
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorLan Ni
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorJian-Zhi Wang
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Search for more papers by this authorFang Wang
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorJian-Guo Chen
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China
Institutes of Biomedcine and Drug Discovery, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China
Search for more papers by this authorSummary
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 H2O2-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.
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