Impaired long term memory consolidation in transgenic mice overexpressing the human soluble form of IL-1ra in the brain

Interleukin-1 (IL-1) is expressed following LTP induction and is required for long-term memory consolidation. We demonstrate that the long-term, but not short-term memory is impaired in a transgenic mouse strain overexpressing the human soluble interleukin-1 receptor antagonist (hsIL-1ra) in the brain. Overexpression of IL-1ra was found to reduce the basal as well as the novelty-induced upregulation of activity-regulated cytoskeleton-associated protein (Arc) in the dentate gyrus and in the retrosplenial cortex. Together with the finding that blocking IL-1 receptors interferes with the BDNF-ERK1/2 pathway, our data suggest an essential role played by physiological levels of IL-1 in long-term memory consolidation. (C) 2009 Elsevier B.V. All rights reserved.