title: Systemic administration of lipopolysaccharide induces cyclooxygenase-2 immunoreactivity in endothelium and increases microglia in the mouse hippocampus.
abstract: In this study, we observed the effects of lipopolysaccharide (LPS) on neurodegeneration and immune response in the hippocampus. LPS is a gram-negative bacterial cell surface proteoglycan and known as a bacterial endotoxin. For this, we investigated the optimal concentration of LPS influencing the ICR mouse hippocampus to measure the LPS receptor, e.g., toll-like receptor 4 (TLR4), expression in mouse hippocampal homogenates. TLR4 expression was significantly and prominently increased in the hippocampal homogenates of the LPS (1 mg/kg)-treated group. Next, we examined pro-inflammatory response in the hippocampus using cyclooxygenase-2 (COX-2, a marker for inflammatory response) immunohistochemistry after LPS treatment. COX-2 immunoreactivity was significantly increased in the endothelium of blood vessels in the hippocampus 6 h after LPS treatment, judging from double immunofluorescence study with platelet-derived endothelial cell adhesion molecule-1 (PECAM-1, a marker for endothelial cells): it decreased 12 h and disappeared 24 h after LPS treatment. In addition, the ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive ((+)) microglia were morphologically activated in the mouse hippocampus after LPS treatment. At 24 h after LPS treatment, Iba-1(+) microglia of activated forms were abundant in the hippocampus. However, NeuN (a neuron-specific soluble nuclear antigen)(+) neurons were not significantly changed in the hippocampus after LPS treatment. Fluoro-jade B (a marker for neuronal degeneration)(+) cells were not detected in the hippocampus at any time after LPS treatment. In addition, there were no significant differences in permeability of blood-brain barriers at any time points after LPS treatment. In brief, our results indicate that intraperitoneal administration of 1 mg/kg LPS effectively induces LPS receptor (TLR4) expression in the hippocampus, and the treatment increases corticosterone levels, inflammation in the blood vessels, and microglial activation in the hippocampus without any neuronal damage.
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Chung
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Chung
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Youn
authors.forename: In Se
authors.initials: IS
authors.lastname: Lee
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007113:Immunity, Innate / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008840:Microfilament Proteins; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010539:Permeability; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051197:Toll-Like Receptor 4; D051546:Cyclooxygenase 2; D003345:Corticosterone