Sodium hydrosulfide attenuates beta-amyloid-induced cognitive deficits and neuroinflammation via modulation of MAPK/NF-κB pathway in rats

Huiyu Liu, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Wenxian Li, Jingshan Shi, Qihai Gong*

*Corresponding author for this work

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Beta-amyloid (Aβ), a neurotoxic peptide, accumulates in the brain of Alzheimer's disease (AD) subjects to initiate neuroinflammation eventually leading to memory impairment. Here, we demonstrated that A beta-injected rats exhibited cognitive impairment and neuroinflammation with a remarkable reduction of hydrogen sulfide (H2S) levels in the hippocampus compared with that in sham-operated rats. Interestingly, the expression of cystathionine-β-synthase (CBS) and 3-mercaptopyruvate-sulfurtransferase (3MST), the major enzymes responsible for endogenous H2S generation, were also significantly decreased. However, intraperitoneal (i.p.) injection of sodium hydrosulfide (NaHS, a H2S donor) dramatically attenuated cognitive impairment and neuroinflammation induced by hippocampal injection of 10 μg of A beta1-42 in rats. Subsequently, NaHS significantly suppressed the expression of tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β) and cyclooxygenase-2 (COX-2) in rat hippocampus following Aβ administration. Furthermore, NaHS exerted a beneficial effect on inhibition of IκB-α degradation and subsequent activation of transcription factor nuclear factor κB (NF-κB), as well as inhibition of extracellular signal-regulated kinase (ERK1/2) activity and p38 MAPK activity but not c-Jun N-terminal kinase (JNK) activity induced by Aβ. These results demonstrate that NaHS might be a potential agent for treatment of neuroinflammation-related AD.

Original languageEnglish
Pages (from-to)673-683
Number of pages11
JournalCurrent Alzheimer Research
Volume12
Issue number7
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • 3-mercaptopyruvate-sulfurtransferase (3MST)
  • Alzheimer's disease
  • beta-amyloid1-42
  • cystathionine-β-synthase (CBS)
  • hydrogen sulfide
  • neuroinflammation

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