Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2

Yuangui Liu; Yuanyuan Deng; Huiyu Liu; Caixia Yin; Xiaohui Li; Qihai Gong

doi:10.1016/j.pbb.2016.11.002

Hydrogen sulfide ameliorates learning memory impairment in APP/PS1 transgenic mice: A novel mechanism mediated by the activation of Nrf2

Pharmacol Biochem Behav. 2016 Nov-Dec:150-151:207-216. doi: 10.1016/j.pbb.2016.11.002. Epub 2016 Nov 21.

Authors

Yuangui Liu¹, Yuanyuan Deng¹, Huiyu Liu¹, Caixia Yin¹, Xiaohui Li¹, Qihai Gong²

Affiliations

¹ Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China.
² Department of Pharmacology and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China. Electronic address: gqh@zmc.edu.cn.

PMID: 27883916
DOI: 10.1016/j.pbb.2016.11.002

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, Aβ_1-40 and Aβ_1-42 levels, 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.

Keywords: Alzheimer's disease; Amyloid beta; Hydrogen sulfide; Nuclear factor erythroid-2-related factor 2; Oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / drug therapy*
Alzheimer Disease / metabolism
Alzheimer Disease / pathology
Amyloid Precursor Protein Secretases / analysis
Amyloid beta-Protein Precursor / analysis
Amyloid beta-Protein Precursor / physiology*
Animals
Antioxidant Response Elements / physiology
Aspartic Acid Endopeptidases / analysis
Cystathionine beta-Synthase / analysis
Hydrogen Sulfide / therapeutic use*
Male
Memory Disorders / drug therapy*
Mice
Mice, Inbred C57BL
Mice, Transgenic
NF-E2-Related Factor 2 / analysis
NF-E2-Related Factor 2 / physiology*
Oxidative Stress / drug effects
Presenilin-1 / physiology*
Sulfurtransferases / analysis

Substances

Amyloid beta-Protein Precursor
NF-E2-Related Factor 2
Nfe2l2 protein, mouse
Presenilin-1
Sulfurtransferases
3-mercaptopyruvate sulphurtransferase
Amyloid Precursor Protein Secretases
Aspartic Acid Endopeptidases
Bace1 protein, mouse
Cystathionine beta-Synthase
Hydrogen Sulfide