title: Hydrogen Sulfide Prevents Synaptic Plasticity from VD-Induced Damage via Akt/GSK-3β Pathway and Notch Signaling Pathway in Rats.
abstract: Our previous study has demonstrated that hydrogen sulfide (H2S) attenuates neuronal injury induced by vascular dementia (VD) in rats, but the mechanism is still poorly understood. In this study, we aimed to investigate whether the neuroprotection of H2S was associated with synaptic plasticity and try to interpret the potential underlying mechanisms. Adult male Wistar rats were suffered the ligation of bilateral common carotid arteries. At 24 h after surgery, rats were administered intraperitoneally with sodium hydrosulfide (NaHS, 5.6 mg·kg(-1)·day(-1)), a H2S donor, for 3 weeks in the VD+NaHS group and treated intraperitoneally with saline in the VD group respectively. Our results demonstrated that NaHS significantly decreased the level of glutamate. It obviously ameliorated cognitive flexibility as well as the spatial learning and memory abilities by Morris water maze. Moreover, NaHS significantly improved the long-term depression (LTD), and was able to elevate the expression of N-methyl-D-aspartate receptor subunit 2A, which plays a pivotal role in synaptic plasticity. Interestingly, NaHS decreased the phosphorylation of Akt, and it could maintain the activity of glycogen synthase kinase-3β (GSK-3β). Surprisingly, NaHS triggered the canonical Notch pathway by increasing expressions of Jagged-1 and Hes-1. These findings suggest that NaHS prevents synaptic plasticity from VD-induced damage partly via Akt/GSK-3β pathway and Notch signaling pathway.Hydrogen sulfide modulated the ratio of NMDAR 2A/2B and improved the synaptic plasticity via Akt/GSK-3β pathway and Notch signaling pathway in VD rats.
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
authors.forename: Xiaxia
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, 94 Weijin Road, Tianjin, 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D015140:Dementia, Vascular / Q000473:pathology* / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D065853:Spatial Learning / Q000187:drug effects; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D051880:Receptors, Notch; D018698:Glutamic Acid; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
keywords: Hippocampus; Hydrogen sulfide; Long-term depression; Vascular dementia