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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)


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, 2.8 mg/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, Aβ1–40 and Aβ1–42 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.
Original languageEnglish
Pages (from-to)207-216
Number of pages10
JournalPharmacology Biochemistry and Behavior
Publication statusPublished - Nov 2016
Externally publishedYes

Bibliographical note

A corrigendum exists for this article and can be found in Pharmacology Biochemistry and Behavior (2017) Vol 153 p.191 at doi: 10.1016/j.pbb.2016.12.004


  • Hydrogen sulfide
  • Alzheimer's disease
  • Oxidative stress
  • Amyloid beta
  • Nuclear factor erythroid-2-related factor 2


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