Sodium Hydrosulfide Attenuates Beta-Amyloid-Induced Cognitive Deficits and Neuroinflammation via Modulation of MAPK/NF-κB Pathway in Rats

Author(s): Huiyu Liu, Yuanyuan Deng, Jianmei Gao, Yuangui Liu, Wenxian li, Jingshan Shi, Qihai Gong.

Journal Name: Current Alzheimer Research

Volume 12 , Issue 7 , 2015

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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 Aβ-injected rats exhibited cognitive impairment and neuroinflammation with a remarkable reduction of hydrogen sulfide (H2S) levels in the hippocampus compared with that in shamoperated 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 Aβ1-42 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.

Keywords: 3-mercaptopyruvate-sulfurtransferase (3MST), Alzheimer’s disease, beta-amyloid1-42, cystathionine-β-synthase (CBS), hydrogen sulfide, neuroinflammation.

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Article Details

VOLUME: 12
ISSUE: 7
Year: 2015
Page: [673 - 683]
Pages: 11
DOI: 10.2174/1567205012666150713102326
Price: $58

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