期刊
NEUROSCIENCE
卷 164, 期 4, 页码 1484-1495出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2009.08.073
关键词
neuroinflammation; water maze; IL-1 beta(XAT) transgenic mouse; hippocampus
资金
- Clare Boothe Luce Foundation
- NIH [RO3MH069746, RO1AG030149]
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 age-related dementia. Few studies have investigated the impact of sustained elevation of hippocampal interleukin-1 beta, a pro-inflammatory cytokine upregulated during aging and Alzheimer's disease, on cognition in mice. We utilized the IL-1 beta(XAT) transgenic mouse to initiate bilateral hippocampal overexpression of interleukin-1 beta to determine the influence of sustained neuroinflammation independent of disease pathology. Fourteen days following transgene induction, adult male and female IL-1 beta(XAT) mice were tested on non-spatial and spatial versions of the Morris water maze. For the spatial component, one retention trial was conducted 48 h after completion of a 3 day acquisition protocol (eight trials per day). Induction of IL-1 beta 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-1 beta(XAT) transgenic mice to investigate chronic neuroinflammation in age- and pathology-related cognitive dysfunction. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
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