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-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. © 2012 xuan et al.; licensee biomed central ltd.