Role of microglial IKKβ in kainic acid-induced hippocampal neuronal cell death

Ik Hyun Cho, Jinpyo Hong, Eun Cheng Suh, Jae Hwan Kim, Hyunkyoung Lee, Jong Eun Lee, Soojin Lee, Chong Hyun Kim, Dong Woon Kim, Eun Kyeong Jo, Kyung Eun Lee, Michael Karin, Sung Joong Lee

Research output: Contribution to journalArticlepeer-review

140 Scopus citations


Microglial cells are activated during excitotoxin-induced neurodegeneration. However, the in vivo role of microglia activation in neurodegeneration has not yet been fully elucidated. To this end, we used Ikkβ conditional knockout mice (LysM-Cre/IkkβF/F) in which the Ikkβ gene is specifically deleted in cells of myeloid lineage, including microglia, in the CNS. This deletion reduced IκB kinase (IKK) activity in cultured primary microglia by up to 40% compared with wild-type (IkkβF/F), and lipopolysaccharide-induced proinflammatory gene expression was also compromised. Kainic acid (KA)-induced hippocampal neuronal cell death was reduced by 30% in LysM-Cre/IkkβF/F mice compared with wild-type mice. Reduced neuronal cell death was accompanied by decreased KA-induced glial cell activation and subsequent expression of proinflammatory genes such as tumour necrosis factor (TNF)-α and interleukin (IL)-1β. Similarly, neurons in organotypic hippocampal slice cultures (OHSCs) from LysM-Cre/IkkβF/F mouse brain were less susceptible to KA-induced excitotoxicity compared with wild-type OHSCs, due in part to decreased TNF-α and IL-1β expression. Based on these data, we concluded that IKK/nuclear factor-κB dependent microglia activation contributes to KA-induced hippocampal neuronal cell death in vivo through induction of inflammatory mediators.

Original languageEnglish
Pages (from-to)3019-3033
Number of pages15
Issue number11
StatePublished - Nov 2008

Bibliographical note

Funding Information:
Neurobiology Research Program at the Korea Ministry of Science and Technology, Republic of Korea (M10412000014-07N1200-01410); Korea Research Foundation Grant (KRF-2005-070-C00096). National Institutes of Health grants for Knockout mouse generation in San Diego (ES04151, ES006376 and AI043477); Korea Research Foundation Grant funded by the Korean Government (MOEHRD, KRF-2006-351-E00016 to I.-H.Cho).


  • Excitotoxicity
  • Hippocampus
  • IKKβKainic acid
  • Microglia


Dive into the research topics of 'Role of microglial IKKβ in kainic acid-induced hippocampal neuronal cell death'. Together they form a unique fingerprint.

Cite this