Hydrogen sulfide alleviates lipopolysaccharide‐induced memory impairment, neurodegeneration and neuroinflammation in Swiss albino mice

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a major neurodegenerative disorder characterized by Aβ‐plaque deposition, formation of neurofibrillary tangles, neuroinflammation, and neurodegeneration. Although not the initiator of the disease, neuroinflammation has been known to play a pivotal role in the pathogenesis of AD. Neuroinflammation was induced by systemic lipopolysaccharide (LPS), which expresses a cascade of enzymes leading to tau hyperphosphorylation and deposition of β‐amyloid plaques, ultimately leading to cell apoptosis. Hydrogen sulfide (H2S) has been reported to have anti‐inflammatory and neuroprotective activity, though the exact mechanism for its effect has not been explored. Thus, Sodium hydrosulfide (NaHS), a known H2S donor, was used to determine the mechanism of its neuroprotective activity in LPS‐induced apoptosis and neuroinflammation in mice.MethodNaHS (2.5, 5, and 10 mg/kg i.p.) was administered to Swiss albino mice for 28 days. From 15th day, LPS (0.25mg/kg i.p.) was administered for 7 days along with NaHS. Memory impairment was evaluated by using Morris Water Maze (MWM) task and Y‐maze task. At the end of the experiment, animals were euthanized and brain tissue homogenates were used for evaluating biochemical parameters. Brain tissue homogenates were evaluated for anti‐apoptotic (c‐Jun and Caspase‐3), anti‐inflammatory (TNF‐α and IL‐6), antioxidant [Glutathione (GSH), superoxide dismutase (SOD) and lipid peroxidation (LPO)], and Acetylcholinesterase (AChE) activities.ResultLPS administration significantly increased neurodegeneration and caused cognitive impairment in mice. NaHS lead to improved basal memory retention in MWM and Y‐maze tasks. Treatment with NaHS attenuated LPO which was induced by LPS. NaHS normalized the decreased levels of GSH in LPS treated groups. However, NaHS administration failed to significantly prevent increase in AChE activity. The activity of superoxide dismutase was significantly increased in NaHS + LPS treated groups. LPS upregulated c‐Jun and Caspase‐3 levels and NaHS prevented it. Increase in the expression of proinflammatory cytokines (TNF‐α and IL‐6) were significantly alleviated by NaHS treatment.ConclusionH2S treatment significantly attenuates LPS‐induced oxidative stress, memory deficit, neurodegeneration, and neuroinflammation. The results indicate that H2S is effective in providing protection against neurodegeneration and H2S containing hybrids can be explored further for their potential clinical use as prophylactic and symptomatic therapy in AD.