EN
Our recent data have shown that systemic infl ammation evoked by lipopolysaccharide (LPS) stimulates NO-mediated signalling pathways in the midbrain. The aim of the present study was to investigate the dynamics of proinfl ammatory genes expression in mouse hippocampus during 4 days after intraperitoneal injection of LPS (1 mg/kg b.w.). Moreover, the selected biochemical processes involved in cell death pathways were analysed. Real-time PCR analysis indicated the signifi cant time-dependent alteration of several prooxidative genes expression. During fi rst 3 h posttreatment the level of mRNA for COX-2, iNOS and TNFα was increased, then after 6–24 h for cPLA2, TLR4, 5-LOX and 12- LOX, respectively. Immunohistochemical analysis showed an appearance of many activated microglia cells, confi rming activation of local infl ammatory reaction in hippocampus. The biochemical and molecular studies demonstrated the signifi cant activation of apoptosis inducing factor (AIF)-mediated, caspase-3 -independent death signalling and cathepsin B-related autophagy. These data were confi rmed by electron-microscopic examination of cell ultrastructure. The presented genetic, biochemical and morphologic alterations induced by systemic infl ammation could be responsible for impairment of learning and memory. This study was supported by Scientifi c Network 28/E-32/BWSN-0053/2008.