Increased cyclooxygenase-2 and nuclear factor-κB/p65 expression in mouse hippocampi after systemic administration of tetanus toxin

Yan,Bing  Chun; Jeon,Yong  Hwan; Park,Joon  Ha; Kim,In  Hye; Cho,Jeong‑Hwi; Ahn,Ji  Hyeon; Chen,Bai  Hui; Tae,Hyun‑Jin; Lee,Jae‑Chul; Ahn,Ji  Yun; Kim,Dong  Won; Cho,Jun  Hwi; Won,Moo‑Ho; Hong,Seongkweon

doi:10.3892/mmr.2015.4490

Increased cyclooxygenase-2 and nuclear factor-κB/p65 expression in mouse hippocampi after systemic administration of tetanus toxin

Authors:
- Bing Chun Yan
- Yong Hwan Jeon
- Joon Ha Park
- In Hye Kim
- Jeong‑Hwi Cho
- Ji Hyeon Ahn
- Bai Hui Chen
- Hyun‑Jin Tae
- Jae‑Chul Lee
- Ji Yun Ahn
- Dong Won Kim
- Jun Hwi Cho
- Moo‑Ho Won
- Seongkweon Hong
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Affiliations: Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu 225001, P.R. China, Department of Radiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea, Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea, Department of Physiology, College of Medicine, Hallym University, Chuncheon, Gangwon 200‑702, Republic of Korea, Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon, Gangwon 200‑702, Republic of Korea, Department of Emergency Medicine, Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Gyeonggi 431‑796, Republic of Korea, Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea, Department of Surgery, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
Published online on: October 26, 2015 https://doi.org/10.3892/mmr.2015.4490
Pages: 7837-7844
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Brain inflammation has a crucial role in various diseases of the central nervous system. The hippocampus in the mammalian brain exerts an important memory function, which is sensitive to various insults, including inflammation induced by exo/endotoxin stimuli. Tetanus toxin (TeT) is an exotoxin with the capacity for neuronal binding and internalization. The present study investigated changes in inflammatory mediators in the mouse hippocampus proper (CA1‑3 regions) and dentate gyrus (DG) after TeT treatment. The experimental mice were intraperitoneally injected with TeT at a low dosage (100 ng/kg), while the control mice were injected with the same volume of saline. At 6, 12 and 24 h after TeT treatment, changes in the hippocampal levels of inflammatory mediators cyclooxygenase‑2 (COX‑2) and nuclear factor kappa‑B (NF‑κB/p65) were assessed using immunohistochemical and western blot analysis. In the control group, moderate COX‑2 immunoreactivity was observed in the stratum pyramidal (SP) of the CA2‑3 region, while almost no expression was identified in the CA1 region and the DG. COX‑2 immunoreactivity was increased by TeT in the SP and granule cell layer (GCL) of the DG in a time‑dependent manner. At 24 h post‑treatment, COX‑2 immunoreactivity in the SP of the CA1 region and in the GCL of the DG was high, and COX‑2 immunoreactivity in the SP of the CA2/3 region was highest. Furthermore, the present study observed that NF‑κB/p65 immunoreactivity was obviously increased in the SP and GCL at 6, 12 and 24 h after TeT treatment. In conclusion, the present study demonstrated that systemic treatment with TeT significantly increased the expression of COX-2 and NF-κB/p65 in the mouse hippocampus, suggesting that increased COX‑2 and NF-κB/65 expression may be associated with inflammation in the brain induced by exotoxins.

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