IL-1RA blocks E. coli-induced suppression of Arc and long-term memory in aged F344 x BN F1 rats

In normal aging, a peripheral immune challenge induces a sensitized and protracted neuroinflammatory response in parallel with long-term memory (LTM) impairments. Pro-inflammatory mediators of neuro-inflammation impair LTM, synaptic plasticity and LTP. The immediate early gene Arc is considered a critical protein regulating LTM and synaptic plasticity. The present investigation examined whether (1) a peripheral Escherichia coli infection suppresses hippocampal Arc expression, and (2) central pro-inflammatory cytokines (IL-1 beta and IL-6) mediate the effects of peripheral E. coli infection on Arc and LTM. In 24 months F344 x BN F1 rats, E. coli infection suppressed basal Arc gene expression as well as contextual fear conditioning-induced Arc expression. E. coli treatment failed to alter either basal or conditioning-induced c-Fos expression. At 24 h post-infection, intra-cisterna magna (ICM) treatment with the anti-inflammatory cytokine IL-1RA blocked the E. coli-induced suppression of hippocampal Arc and increases in IL-6 protein. At 4-day post-infection, IL-1RA blocked the E. coli-induced LTM impairments and increases in IL-6 protein. The present results suggest that central pro-inflammatory cytokines play a salient role in the suppression of Arc and impairments of LTM by a peripheral immune challenge in older animals. (C) 2009 Elsevier Inc. All rights reserved.