Sustained hippocampal IL-1β overexpression impairs contextual and spatial memory in transgenic mice

Neuroinflammatory conditions such as traumatic brain injury, aging, Alzheimer's disease, and Down syndrome are often associated with cognitive dysfunction. Much research has targeted inflammation as a causative mediator of these deficits, although the diverse cellular and molecular changes that accompany these disorders obscure the link between inflammation and impaired memory. Therefore, we used a transgenic mouse model with a dormant human IL-1 beta excisional activation transgene to direct overexpression of IL-1 beta with temporal and regional control. Two weeks of hippocampal IL-1 beta overexpression impaired long-term contextual and spatial memory in both male and female mice, while hippocampal-independent and short-term memory remained intact. Human IL-1 beta overexpression activated glia, elevated murine IL-1 beta protein and PGE(2) levels, and increased pro-inflammatory cytokine and chemokine mRNAs specifically within the hippocampus, while having no detectable effect on inflammatory mRNAs in the liver. Sustained neuroinflammation also reduced basal and conditioning-induced levels of the plasticity-related gene Arc. (C) 2009 Elsevier Inc. All rights reserved.