Abstract
Hydrogen sulfide (H2S) is reported to have a neuroprotective activity; however, the role of H2S in neuroinflammation-induced neuronal damage is ambiguous. Here, we aimed to evaluate the underlying mechanisms for the neuroprotective effect of NaHS, a known H2S donor, against lipopolysaccharide (LPS)-induced memory impairment (MI). All the treatments were administered for 28 days, and LPS (0.25 mg/kg i.p.) was co-administered intermittently for 7 days from days 15 to 21. Morris water maze (MWM) and Y-maze tests were performed to evaluate MI. Neurodegeneration was histopathologically examined, and the brain homogenates were characterized for reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-6, caspase-3, c-Jun, and acetylcholinesterase (AChE) by biochemical analysis. H2S administration significantly improved spatial and working memory in MWM and Y-maze tasks, respectively. Exogenous H2S significantly reversed LPS-induced oxidative stress as evidenced by improved GSH, MDA, and SOD levels. H2S pretreatment significantly attenuated LPS-induced apoptosis and inflammation by decreasing c-Jun and caspase-3 levels and inhibiting TNF-α and IL-6, respectively. The decrease in these markers was supported by H&E and Nissl staining, which confirmed the anti-necrotic activity of H2S. However, there was no significant improvement in LPS-induced increase in AChE activity. These results indicate that chronic systemic inflammation leads to neurodegeneration and MI and H2S exerts its neuroprotective effect due to its anti-oxidative, anti-inflammatory, and anti-apoptotic potential via modulation of JNK and extrinsic apoptosis pathways.
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The authors would like to acknowledge the help of Dr. S. J. Pawar (M.V.Sc. Veterinary pathology) for histopathological examinations of brain samples.
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The research was supported by the All India Council for Technical Education (AICTE), New Delhi, India.
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Kshirsagar, V., Thingore, C., Gursahani, M. et al. Hydrogen Sulfide Ameliorates Lipopolysaccharide-Induced Memory Impairment in Mice by Reducing Apoptosis, Oxidative, and Inflammatory Effects. Neurotox Res 39, 1310–1322 (2021). https://doi.org/10.1007/s12640-021-00374-6
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DOI: https://doi.org/10.1007/s12640-021-00374-6