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

Title
Role of microglial IKKβ in kainic acid-induced hippocampal neuronal cell death
Authors
Cho I.-H.Hong J.Suh E.C.Kim J.H.Lee H.Lee J.E.Lee S.Kim C.-H.Kim D.W.Jo E.-K.Lee K.E.Karin M.Lee S.J.
Ewha Authors
이경은
SCOPUS Author ID
이경은scopus
Issue Date
2008
Journal Title
Brain
ISSN
0006-8950JCR Link
Citation
vol. 131, no. 11, pp. 3019 - 3033
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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. © The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
DOI
10.1093/brain/awn230
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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