title: Hydrogen sulfide improves spatial memory impairment and decreases production of Aβ in APP/PS1 transgenic mice.
abstract: Alzheimer's disease (AD) is defined both by its progressive cognitive deterioration and hallmark increase in neuronal Aβ plaque formation. However, many of the underlying neurobiological facets of this disease are still being elucidated. Previous research has demonstrated that production of neuronal hydrogen sulfide (H2S) is significantly decreased in patients with AD. Moreover, systemic plasma H2S levels are negatively correlated with its severity. However, how a decrease in H2S production might be correlated with either the etiology or pathophysiology of AD remains unknown. To better understand the role of H2S in AD, we examined both levels of H2S and the expression and activity H2S-synthesizing enzyme (cystathionine beta synthase or CBS) in an APP/PS1 transgenic mouse line at 3, 6, 9 and 12 months. After intraperitoneal (i.p.) administration of an H2S donor (NaHS) into APP/PS1 mice, application of exogenous H2S resulted in improved spatial learning and memory acquisition in APP/PS1 mice. H2S administration also led to significant decrease in extracellular levels of Aβ40 and Aβ42, the expression of BACE1 and PS1, and a significant increase of ADAM17 expression. Similarly, an increase in non-amyloidogenic C83 fragment generation and a decrease in amyloidogenic C99 fragment generation were also observed. Thus, NaHS application resulted in a shift from the plaque-forming beta pathway to the non-plaque forming alpha pathway of APP cleavage in 6 and 12 month APP/PS1 mice. These results indicate the importance of H2S to AD severity and that administration of exogenous H2S can promote a non-amyloidogenic processing of APP.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors.forename: Xuan-Li
authors.initials: XL
authors.lastname: He
authors.affiliation: Department of Neurology, The University-Town Hospital of Chongqing Medical University, Chongqing 401331, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors.forename: Yun-Wen
authors.initials: YW
authors.lastname: Qi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China.
authors.forename: Meng-Jie
authors.initials: MJ
authors.lastname: Liu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing 400016, China. Electronic address: ywxlh@aliyun.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
mesh_terms: D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D018782:Maze Learning; D008569:Memory Disorders / Q000188:drug therapy*; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1; C580804:presenilin 1, mouse; D006862:Hydrogen Sulfide
keywords: A disintegrin metalloprotease; Alzheimer’s disease; Amyloid beta; Beta-site amyloid precursor protein cleaving enzyme 1; Hydrogen sulfide; Presenilin 1