Differential nuclear factor-kappa B phosphorylation induced by lipopolysaccharide in the hippocampus of P2X7 receptor knockout mouse. (May 2013)

• Record Type: Journal Article
• Authors: Kim, Won Il; Ryu, Hea Jin; Kim, Ji-Eun; Seo, Cheong Hoon; Lee, Boung Chul; Choi, Ihn-Geun; Kang, Tae-Cheon
• Is Part Of: Neurological research. Volume 35:Number 4(2013)
• Page Start: 369
• Page End: 381
• Publication Date: 2013-05
• Subjects: LPS -- Neuronal damage -- NF-kappaB -- Phosphorylation -- P2X7 knockout mouse; Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8005
• DOI: 10.1179/1743132812Y.0000000137
• Languages: English
• ISSNs: 0161-6412

Abstract

Abstract : Objective: Lipopolysaccharide (LPS) stimulates the innate immune response in the brain through nuclear factor-kappaB (NF-kappaB) signaling. Since purinergic signals activate NF-kappaB through the P2X7 receptor (P2X7R), we investigated the roles of P2X7R in neuronal NF-kappaB phosphorylation in the mouse hippocampus under basal conditions and P2X7R deletion following LPS treatment in vivo . Methods: We performed immunohistochemical studies for neuronal NF-kappaB phosphorylation in the hippocampi of wild type (WT) and P2X7R knockout (KO) mice under basal conditions and LPS treatment. Results: LPS treatment did not induce neuronal damages in both WT and P2X7 −/− KO mice. In WT animals, LPS treatment increased p65-Ser276 and p65-Ser311 NF-kappaB phosphorylations in hippocampal neurons. However, p52-Ser865, p52-Ser869, p65-Ser468, p65-Ser529, and p65-Ser536 NF-kappaB phosphorylations were unaffected by LPS treatment. In P2X7 −/− KO mice, neuronal p65-Ser311 NF-kappaB phosphorylation in vehicle-treated animals was higher than that in WT animals. In addition, both p65-Ser276 and p65-Ser311 NF-kappaB phosphorylations were unaffected by LPS treatment in P2X7 −/− KO mice. Discussion: These findings indicate that P2X7R may be involved in LPS-induced inflammatory response in neurons, and that p65-Ser311 NF-kappaB phosphorylation may compensate for the loss function of P2X7R by as yet unknown factors.