title: S-propargyl-cysteine, a novel hydrogen sulfide-modulated agent, attenuates lipopolysaccharide-induced spatial learning and memory impairment: involvement of TNF signaling and NF-κB pathway in rats.
abstract: Neuroinflammation exacerbates hyperphosphorylated tau and amyloid-β (Aβ) generation by generating a plethora of inflammatory mediators and neurotoxic compounds in a transgenic model of Alzheimer's disease (AD), and it was reported that hydrogen sulfide (H₂S) attenuates lipopolysaccharide (LPS)-induced neuroinflammation both in vitro and in vivo. In the present study, the protective effects of S-propargyl-cysteine (SPRC) on spatial learning and memory impairment induced by LPS were examined in vivo, and the possible mechanisms were explored. The data showed that SPRC administration by intraperitoneal (i.p.) injection may attenuate cognitive impairment induced by bilateral intracerebroventricular (b.i.c.v.) injection of 5 μg of LPS in rats. Subsequently, SPRC prevented a decrease of H₂S levels in rat hippocampus subjected to LPS. Furthermore, SPRC afforded beneficial actions in inhibitions tumor necrosis factor (TNF)-α, TNF-α receptor 1 (TNFR1) and Aβ generation, as well as IκB-α degradation and phospho-transcription factors of the nuclear factor κB p65 (p-NF-κB p65) activation induced by LPS. These findings suggested that SPRC, a novel H₂S-modulated agent, might be a potential agent for the treatment of neuroinflammation-related diseases, such as AD.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Qi-Hai
authors.initials: QH
authors.lastname: Gong
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Li-Long
authors.initials: LL
authors.lastname: Pan
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Xin
authors.forename: Yi-Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis; D000818:Animals; D015153:Blotting, Western; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D007859:Learning Disabilities / Q000139:chemically induced* / Q000523:psychology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced* / Q000523:psychology*; D016328:NF-kappa B / Q000502:physiology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D047990:TNF Receptor-Associated Factor 1 / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C556437:S-propargylcysteine; D047990:TNF Receptor-Associated Factor 1; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D003545:Cysteine; D006862:Hydrogen Sulfide