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

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.

Hydrogen sulfide protects against cognitive impairment induced by hepatic ischemia and reperfusion via attenuating neuroinflammation

“…This is in line with previous report suggesting that NaHS could attenuate neuroinflammation in the hippocampus. 15 On the other hand, our data suggested that hepatic I/R could induce cognitive decline in rats and treatment with NaHS efficiently ameliorated such cognitive deficits. In sum, these results suggest NaHS alleviates hepatic I/R-induced cognitive impairment via inhibiting neuroinflammation, and NaHS has a significant anti-inflammatory effect in the central nervous system.…”

“…In addition, another study has demonstrated that NaHS could attenuate neuroinflammation and neuronal injury in brain. 15 Taken together, we speculated that NaHS protected against hepatic I/Rinduced cognitive deficits that are associated with reduced peripheral proinflammatory cytokines entering the brain and decreased local brain inflammation response and neuronal damages.…”

“…14 Furthermore, in the brain, H 2 S has been shown to suppress hippocampal neuroinflammation and to alleviate memory deficits. 15 The ability of H 2 S to enhance N-methyl-D-aspartate (NMDA) receptors activity and potentiate long-term potentiation (LTP) induction also suggests that H 2 S contributes to the process of learning and memory. 16,17 Previous experiment has demonstrated that H 2 S could alleviate hepatic I/R injury.…”

Hydrogen Sulfide Inhalation Decreases Early Blood—Brain Barrier Permeability and Brain Edema Induced by Cardiac Arrest and Resuscitation

“…metabolism, suppress oxidative stress, have antiinflammatory effects, and shown to be neuroprotective in ischemia/reperfusion injury models of the central nervous system. 5,[27][28][29] We investigated whether inhalation of H 2 S was protective against CA and resuscitation-induced BBB disruption.…”

Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

“…This finding is consistent with previous findings because inflammation has been implicated as a critical mechanism responsible for the progressive nature of neurodegeneration (44,62), and there is an inverse link between an activated transsulfuration pathway and the immune response. In experimental models, H 2 S exerts antineuroinflammatory effects via inhibition of p38/Jun nuclear kinase and NF-κB signaling pathways (63), and the inhibition of CSE by PPG leads to increased inflammation (64). Furthermore, CSE has been shown to be a modulator of oxidative stress in mice (42).…”