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Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus

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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.

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Acknowledgments

The authors would like to thank Mr. Seok Han, Mr. Seung Uk Lee, and Ms. Hyun Sook Kim for their technical help in this study. This work was supported in part by the MRC program of MOST/KOSEF (R13-2005-022-01002-0), and in part by the Regional Core Research Program funded by the Korea Ministry of Education, Science and Technology (Medical & Bio-material Research Center).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Dae Won Chung, In Koo Hwang & In Se Lee

  2. Department of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea

    Dae Won Chung, Jin Young Chung & Hwa Young Youn

  3. Department of Anatomy and Neurobiology, and Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea

    Ki-Yeon Yoo, Choong Hyun Lee, Jung Hoon Choi & Moo-Ho Won

  4. Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, College of Medicine, Hallym University, Chuncheon, 200-702, Korea

    Dae Won Kim & Soo Young Choi

  5. MRC Research Institute, Hallym University, Chuncheon, 200-702, Republic of Korea

    Moo-Ho Won

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  1. Dae Won Chung
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Correspondence to In Koo Hwang or Moo-Ho Won.

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Dae Won Chung and Ki-Yeon Yoo contributed equally to this article.

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Chung, D.W., Yoo, KY., Hwang, I.K. et al. Systemic Administration of Lipopolysaccharide Induces Cyclooxygenase-2 Immunoreactivity in Endothelium and Increases Microglia in the Mouse Hippocampus. Cell Mol Neurobiol 30, 531–541 (2010). https://doi.org/10.1007/s10571-009-9477-0

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