Sustained expression of interleukin-1β in mouse hippocampus impairs spatial memory

Abstract

Glial activation and neuroinflammation occur in neurodegenerative disease and brain injury, however their presence in normal brain aging suggests that chronic neuroinflammation may be a factor in agerelated dementia. Few studies have investigated the impact of sustained elevation of hippocampal interleukin-1β, a pro-inflammatory cytokine upregulated during aging and Alzheimer's disease, on cognition in mice. We utilized the IL-1β XAT transgenic mouse to initiate bilateral hippocampal overexpression of interleukin-1β to determine the influence of sustained neuroinflammation independent of disease pathology. Fourteen days following transgene induction, adult male and female IL-1β XAT mice were tested on non-spatial and spatial versions of the Morris water maze. For the spatial component, one retention trial was conducted forty-eight hours after completion of a 3-day acquisition protocol (8 trials per day). Induction of IL-1β did not impact non-spatial learning, but was associated with delayed acquisition and decreased retention of the spatial task. These behavioral impairments were accompanied by robust reactive gliosis and elevated mRNA expression of inflammatory genes in the hippocampus. Our results suggest that prolonged neuroinflammation response per se may impact mnemonic processes and support the future application of IL-1β XAT transgenic mice to investigate chronic neuroinflammation in age-and pathology-related cognitive dysfunction. Keywordsneuroinflammation; water maze; IL-1β XAT transgenic mouse; hippocampus Chronic neuroinflammation is a prominent feature of Alzheimer's disease (AD) and is believed to contribute to the molecular cascade that ultimately manifests as cognitive dysfunction. It is well known that the single most important risk factor for AD is age. One reason for this association is that the progression from initial pathophysiological event to clinical detection is *Corresponding author: Amy H. Moore, Ph.D., Department of Biology, Carleton College, One North College Street, Northfield, MN 55057, Phone: 1.507.222.5981, Fax: 1.507.222.5757, amoore@carleton.edu. Neuroscience Section Editor: Behavioral Neuroscience Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 December 29. Published in final edited form as:Neuroscience. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript likely to be on the order of decades. Although glial activation is influenced by neuronal plaques and tangles, its presence in the aged brain (Nichols et al., 1993;P...

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