S-Propargyl-cysteine, a novel hydrogen sulfide-modulated agent, attenuates lipopolysaccharide-induced spatial learning and memory impairment: Involvement of TNF signaling and NF-kappa B pathway in rats

Neuroinflammation exacerbates hyperphosphorylated tau and amyloid-beta (A beta) 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 mu g 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)-alpha, TNF-alpha receptor 1 (TNFR1) and A beta generation, as well as I kappa B-alpha degradation and phosphotranscription factors of the nuclear factor kappa B p65 (p-NF-kappa B 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. (C) 2010 Elsevier Inc. All rights reserved.