Abstract
BackgroundEndogenously 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.MethodsWe 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.ResultsWe 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.ConclusionsThese 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.
Highlights
Produced hydrogen sulfide (H2S) may have multiple functions in brain
There was no significant difference in average swim speed among the groups (Figure 1B). These results clearly indicate that NaHS treatment significantly ameliorated severe deficiencies in spatial cognitive performance induced by Aβ1-40
Our results show that NaHS treatment suppressed Aβ1-40-induced activation of p38 mitogen-activated protein kinase (MAPK) and p65 Nuclear factor (NF)-κB but not Jun N-terminal Kinase (JNK), which may contribute to the inhibition of NaHS on the Aβ1-40-induced IL-1β and TNFα production
Summary
Produced hydrogen sulfide (H2S) may have multiple functions in brain. Microglia have been implicated in the progressive nature of numerous neurodegenerative or neuroinflammatory diseases such as AD [1]. Hydrogen sulfide (H2S) is best known as a poisonous gas with an extremely unpleasant odor. It is endogenously produced in the brain from cysteine by cystathionine β-synthase (CBS) and cystathione γ-lyase (CGL) [6]. Numerous studies showed that H2S has anti-oxidant, anti-apoptotic effects in neuron and glial cells [8,9]. Another study showed that H2S is an endogenous anti-inflammatory and neuroprotective agent, and H2S releasing drugs may have therapeutic potential in neurodegenerative disorders of aging such as AD and Parkinson’s disease (PD) [14]
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