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

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-beta(1-40) (A beta(1-40)), and explored possible mechanisms of action. Methods: We injected A beta(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)-1 beta and tumor necrosis factor (TNF)-alpha was measured by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). The expression of A beta(1-40), phospho-p38 mitogen-activated protein kinase (MAPK), phospho-p65 Nuclear factor (NF)-kappa B, 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 A beta(1-40) rat model of AD. NaHS treatment suppressed A beta(1-40)-induced apoptosis in the CA1 subfield of the hippocampus. Moreover, the over-expression in IL-beta(1-40) and TNF-alpha as well as the extensive astrogliosis and microgliosis in the hippocampus induced by A beta(1-40) were significantly reduced following administration of NaHS. Concomitantly, treatment with NaHS alleviated the levels of p38 MAPK and p65 NF-kappa B phosphorylation but not JNK phEndogenouslyosphorylation that occurred in the A beta(1-40)-injected hippocampus. Conclusions: These results indicate that NaHS could significantly ameliorate A beta(1-40)-induced spatial learning and memory impairment, apoptosis, and neuroinflammation at least in part via the inhibition of p38 MAPK and p65 NF-kappa B activity, suggesting that administration of NaHS could provide a therapeutic approach for AD.