The present address of Y. Nolan is Department of Anatomy, University College, Cork, Ireland.
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Activation of c-Jun-N-terminal kinase is critical in mediating lipopolysaccharide-induced changes in the rat hippocampus
Article first published online: 21 FEB 2005
DOI: 10.1111/j.1471-4159.2004.03011.x
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How to Cite
Barry, C. E., Nolan, Y., Clarke, R. M., Lynch, A. and Lynch, M. A. (2005), Activation of c-Jun-N-terminal kinase is critical in mediating lipopolysaccharide-induced changes in the rat hippocampus. Journal of Neurochemistry, 93: 221–231. doi: 10.1111/j.1471-4159.2004.03011.x
Publication History
- Issue published online: 21 FEB 2005
- Article first published online: 21 FEB 2005
- Received October 4, 2004; revised manuscript received November 12, 2004; accepted November 30, 2004.
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Keywords:
- c-jun-N-terminal kinase;
- hippocampus;
- interleukin-1β;
- interleukin-4;
- lipopolysaccharide;
- long-term potentiation
Abstract
Lipopolysaccharide (LPS) exerts a myriad of effects in rat hippocampus; it increases the concentration of the proinflammatory cytokine, interleukin-1β (IL-1β), and signalling via the IL-1 type I receptor (IL-1RI) resulting in phosphorylation of the stress-activated protein kinase, c-jun-N-terminal kinase (JNK) and impairment in long-term potentiation (LTP). This study was designed to establish whether activation of JNK is a pivotal event in mediating the effects of LPS in hippocampus and therefore LPS-treated rats were injected intracerebroventricularly with saline, the JNK inhibitor D-JNKI1, or with the anti-inflammatory cytokine IL-4, which antagonizes the effects of IL-1β upstream of JNK activation. We report that IL-4 blocked the LPS-induced increase in IL-1RI expression and associated increases in phosphorylation of JNK and c-jun, whereas D-JNKI1 inhibited the LPS-induced phosphorylation of c-jun. Both IL-4 and D-JNKI1 inhibited the increase in caspase-3 staining which was associated with LPS treatment, and both abrogated the LPS-induced inhibition of LTP in perforant path-granule cell synapses. The data presented are consistent with the proposal that JNK activation, probably as a result of increased IL-1RI activation, is a critical step in mediating the detrimental effects of LPS in hippocampus.