title: Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2.
abstract: Beta-amyloid (Aβ) plaques and oxidative stress are associated with the pathogenesis of Alzheimer's disease (AD). Hydrogen sulfide (H2S) has been recognized as a cytoprotectant, which improves learning memory impairment and exerts antioxidant effects in neurodegenerative disorders, including AD. The experiment was projected to explore the effects of H2S on cognitive deficits, Aβ levels and possible antioxidant mechanisms. Here, APP/PS1 transgenic mice were injected sodium hydrosulfide (NaHS, a H2S donor, 2.8mg/kg) once a day for three months. It was found that APP/PS1 transgenic mice exhibited cognitive deficits and a large number of senile plaques, along with neurons decrease and Aβ increase. However, intraperitoneal (i.p.) injection of NaHS improved learning memory deficits, decreased the number of senile plaques, Aβ1-40and Aβ1-42levels, suppressed neurons loss, together with up-regulated the levels of cystathionine-β-synthase (CBS) and 3-mercaptopyruvate-sulfurtransferase (3MST). Furthermore, the protein levels of beta-amyloid precursor (APP) and beta-secretase 1 (BACE1) were dramatically restrained after administration of H2S. In addition, H2S exerted antioxidant effects via up-regulation nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and glutathione S-transferase (GST). Taken together, these findings suggest that H2S ameliorates learning memory impairment, decreases the number of senile plaques in APP/PS1 mice possibly through inhibition of Aβ production and activation of Nrf2/antioxidant response element (ARE) pathway.
authors.affiliation: Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China.
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China. Electronic address: gqh@zmc.edu.cn.
authors.forename: Qihai
authors.initials: Q
authors.lastname: Gong
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000032:analysis; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000502:physiology*; D000818:Animals; D061745:Antioxidant Response Elements / Q000502:physiology; D016282:Aspartic Acid Endopeptidases / Q000032:analysis; D003541:Cystathionine beta-Synthase / Q000032:analysis; D006862:Hydrogen Sulfide / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000032:analysis / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects; D053764:Presenilin-1 / Q000502:physiology*; D013466:Sulfurtransferases / Q000032:analysis
chemical_list: D016564:Amyloid beta-Protein Precursor; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D053764:Presenilin-1; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
keywords: Alzheimer's disease; Amyloid beta; Hydrogen sulfide; Nuclear factor erythroid-2-related factor 2; Oxidative stress