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Time-Course Alterations of Toll-Like Receptor 4 and NF-κB p65, and Their Co-Expression in the Gerbil Hippocampal CA1 Region After Transient Cerebral Ischemia

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Abstract

Innate immune system is very important to modulate the host defense against a large variety of pathogens. Toll-like receptors (TLRs) play a key role in controlling innate immune response. Among TLRs, TLR4 is a specific receptor for lipopolysaccharide and associated with the release of pro-inflammatory cytokines. In the present study, we investigated ischemia-related changes of TLR4 immunoreactivity and its protein level, and nuclear factor κB (NF-κB) p65 immunoreactivity regarding inflammatory responses in the hippocampal CA1 region after 5 min of transient cerebral ischemia to identify the correlation between transient ischemia and inflammation. In the sham-operated group, TLR4 immunoreactivity was easily detected in pyramidal neurons of the hippocampal CA1 region (CA1). TLR4 immunoreactivity in pyramidal neurons was distinctively decreased after ischemia/reperfusion (I/R); instead, based on double immunofluorescence study, TLR4 immunoreactivity was expressed in non-pyramidal neurons and astrocytes from 2 days postischemia. In addition, TLR4 protein level was lowest at 1 day postischemia and highest 4 days after I/R. On the other hand, NF-κB p65 immunoreactivity was not detected in the CA1 of the sham-operated group, and NF-κB p65 immunoreactivity was not observed until 1 day after I/R. However, NF-κB p65 immunoreactivity began to be expressed in astrocytes at 2 days postischemia, and the immunoreactivity was strong 4 days postischemia. Our results indicate that TLR4 and NF-κB p65 immunoreactivity are changed in CA1 pyramidal neurons and newly expressed in astrocytes, not in microglia, in the CA1 region after transient cerebral ischemia.

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Acknowledgments

The authors would like to thank Mr. Seok Han, Mr. Seung Uk Lee and Mrs. Hyun Sook Kim for their technical help in this study, and the Korean Basic Science Institute Chuncheon Center for technical assistance with the confocal image analyses (LSM 510 META NLO). This research was supported by the Regional Core Research Program funded by the Korea Ministry of Education, Science and Technology (Medical and Bio-material Research Center), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0009165).

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Authors and Affiliations

  1. Department of Oral Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung, 210-702, South Korea

    Ki-Yeon Yoo

  2. Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea

    Dae Young Yoo & In Koo Hwang

  3. Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Joon Ha Park & Moo-Ho Won

  4. Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul, 151-742, South Korea

    Choong Hyun Lee

  5. Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, 200-701, South Korea

    Jung Hoon Choi

  6. Division of Analytical Bio-imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, 200-701, South Korea

    Seung-Hae Kwon & Song Her

  7. Department of Physiology, and Institute of Neurodegeneration and Neuroregeneration, College of Medicine, Hallym University, Chuncheon, 200-702, South Korea

    Yun Lyul Lee

  8. MRC Research Institute, Hallym University, Chuncheon, 200-702, South Korea

    Yun Lyul Lee & Moo-Ho Won

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  1. Ki-Yeon Yoo
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Correspondence to In Koo Hwang or Moo-Ho Won.

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

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Yoo, KY., Yoo, D.Y., Hwang, I.K. et al. Time-Course Alterations of Toll-Like Receptor 4 and NF-κB p65, and Their Co-Expression in the Gerbil Hippocampal CA1 Region After Transient Cerebral Ischemia. Neurochem Res 36, 2417–2426 (2011). https://doi.org/10.1007/s11064-011-0569-0

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  • DOI: https://doi.org/10.1007/s11064-011-0569-0

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