• Aiguo Xuan, Dahong Long, Jianhua Li, Weidong Ji, Meng Zhang, Lepeng Hong, and Jihong Liu.
• Department of Anatomy, Guangzhou Medical University, Guangzhou, China. xag2005@sohu.com
• J Neuroinflamm. 2012 Aug 17; 9: 202.

BackgroundEndogenously produced hydrogen sulfide (H(2)S) 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 H(2)S donor) on cognitive impairment and neuroinflammatory changes induced by injections of Amyloid-β(1-40) (Aβ(1-40)), and explored possible mechanisms of action.MethodsWe injected Aβ(1-40) 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 Aβ(1-40), 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.ResultsWe demonstrated that pretreatment with NaHS ameliorated learning and memory deficits in an Aβ(1-40) rat model of AD. NaHS treatment suppressed Aβ(1-40)-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 Aβ(1-40) 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 Aβ(1-40)-injected hippocampus.ConclusionsThese results indicate that NaHS could significantly ameliorate Aβ(1-40)-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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