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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Research

Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in beta-amyloid rat model of Alzheimer’s disease

Authors: Aiguo Xuan, Dahong Long, Jianhua Li, Weidong Ji, Meng Zhang, Lepeng Hong, Jihong Liu

Published in: Journal of Neuroinflammation | Issue 1/2012

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Abstract

Background

Endogenously produced hydrogen sulfide (H2S) may have multiple functions in brain. An increasing number of studies have demonstrated its anti-inflammatory effects. In the present study, we investigated the effect of sodium hydrosulfide (NaHS, a H2S donor) on cognitive impairment and neuroinflammatory changes induced by injections of Amyloid-β1-40 (Aβ1-40), and explored possible mechanisms of action.

Methods

We injected Aβ1-40 into the hippocampus of rats to mimic rat model of Alzheimer’s disease (AD). Morris water maze was used to detect the cognitive function. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to detect neuronal apoptosis. Immunohistochemistry analyzed the response of glia. The expression of interleukin (IL)-1β and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of Aβ1-40, phospho-p38 mitogen-activated protein kinase (MAPK), phospho-p65 Nuclear factor (NF)-κB, and phospho-c-Jun N-terminal Kinase (JNK) was analyzed by western blot.

Results

We demonstrated that pretreatment with NaHS ameliorated learning and memory deficits in an Aβ1-40 rat model of AD. NaHS treatment suppressed Aβ1-40-induced apoptosis in the CA1 subfield of the hippocampus. Moreover, the over-expression in IL-1β and TNF-α as well as the extensive astrogliosis and microgliosis in the hippocampus induced by Aβ1-40 were significantly reduced following administration of NaHS. Concomitantly, treatment with NaHS alleviated the levels of p38 MAPK and p65 NF-κB phosphorylation but not JNK phosphorylation that occurred in the Aβ1-40-injected hippocampus.

Conclusions

These results indicate that NaHS could significantly ameliorate Aβ1-40-induced spatial learning and memory impairment, apoptosis, and neuroinflammation at least in part via the inhibition of p38 MAPK and p65 NF-κB activity, suggesting that administration of NaHS could provide a therapeutic approach for AD.
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Metadata
Title
Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in beta-amyloid rat model of Alzheimer’s disease
Authors
Aiguo Xuan
Dahong Long
Jianhua Li
Weidong Ji
Meng Zhang
Lepeng Hong
Jihong Liu
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-202

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