title: Activity-Dependent Sulfhydration Signal Controls N-Methyl-D-Aspartate Subtype Glutamate Receptor-Dependent Synaptic Plasticity via Increasing d-Serine Availability.
abstract: OBJECTIVE
  Reactive sulfur species, including hydrogen sulfide (H2S) and its oxydates, have been raised as novel redox signaling molecules. The present study aimed at examining whether endogenous sulfhydration signal is required for long-term potentiation (LTP), a cellular model for memory.
  
  
  RESULTS
  In this study, we found that increased synaptic activity triggered sulfide generation and protein sulfhydration. Activity-triggered sulfide production was essential for N-methyl-D-aspartate subtype glutamate receptor (NMDAR)-dependent LTP via maintaining the availability of d-serine, a primary coagonist for synaptic NMDARs. Genetic knockdown of cystathionine β-synthase, not cystathionine γ-lyase, impaired LTP. H2S increased NMDAR-dependent LTP via sulfhydration and disinhibition of serine racemase (SR), a main synthetase of d-serine. We found that polysulfides also increased NMDAR-dependent LTP and NMDAR activity. In aged rats, the level of H2S and SR sulfhydration decreased significantly. Exogenous supplement of H2S restored the sulfhydration of SR, followed by the improvement of age-related deficits in LTP. Furthermore, boost of H2S signal in vivo improves hippocampus-dependent memory. Innovation and Conclusion: Our results provide a direct evidence for the biological significance of endogenous sulfhydration signal in synaptic plasticity. Exogenous supplement of H2S could be considered as the new therapeutic approach for the treatment of neurocognitive dysfunction after aging. Antioxid. Redox Signal. 27, 398-414.
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Yuan-Long
authors.initials: YL
authors.lastname: Li
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .|2 Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation (Huazhong University of Science and Technology) , Wuhan, China .|3 Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology , Wuhan, China .|4 Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China , Wuhan, China .
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wu
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .|2 Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation (Huazhong University of Science and Technology) , Wuhan, China .|3 Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology , Wuhan, China .|4 Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China , Wuhan, China .|5 The Collaborative Innovation Center for Brain Science , Wuhan, China .
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
authors.affiliation: 6 School of Life Science and Technology, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Han
authors.affiliation: 7 Department of Pharmaceutics, College of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Xin-Lei
authors.initials: XL
authors.lastname: Guan
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .|2 Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation (Huazhong University of Science and Technology) , Wuhan, China .|3 Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology , Wuhan, China .|4 Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China , Wuhan, China .
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Long
authors.affiliation: 7 Department of Pharmaceutics, College of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .
authors.forename: Jian-Geng
authors.initials: JG
authors.lastname: Huang
authors.affiliation: 1 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China .|2 Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation (Huazhong University of Science and Technology) , Wuhan, China .|3 Laboratory of Neuropsychiatric Diseases, The Institute of Brain Research, Huazhong University of Science and Technology , Wuhan, China .|4 Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China , Wuhan, China .|5 The Collaborative Innovation Center for Brain Science , Wuhan, China .
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D003541:Cystathionine beta-Synthase / Q000235:genetics; D055785:Gene Knockdown Techniques; D006862:Hydrogen Sulfide / Q000378:metabolism*; D017774:Long-Term Potentiation; D008297:Male; D019998:Racemases and Epimerases / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology; D000099300:Serine Racemase
chemical_list: D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D013440:Sulfides; D000099300:Serine Racemase; C032915:polysulfide
keywords: cystathionine β-synthase; hydrogen sulfide; serine racemase; sulfhydration; synaptic plasticity