Sustained expression of interleukin-1beta in mouse hippocampus impairs spatial memory.
Sustained expression of interleukin-1beta in mouse hippocampus impairs spatial memory.
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DOI：
10.1016/j.neuroscience.2009.08.073
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发表时间：
2009-12-29
期刊：
影响因子：
3.3
通讯作者：
O'Banion, M. K.
中科院分区：
文献类型：
--
作者：
Moore, A. H.;Wu, M.;Shaftel, S. S.;Graham, K. A.;O'Banion, M. K.
神经胶质激活和神经炎症发生在神经退行性疾病和脑损伤中，然而它们在正常大脑衰老中的存在表明慢性神经炎症可能是年龄相关性痴呆的一个因素。很少有研究调查海马白介素-1β持续升高对小鼠认知的影响，白介素-1β是一种在衰老和阿尔茨海默病期间上调的促炎细胞因子。我们利用IL-1βXAT转基因小鼠启动双侧海马过表达白介素-1β，以确定独立于疾病病理的持续神经炎症的影响。转基因诱导14天后，对成年雄性和雌性IL-1βXAT小鼠进行非空间和空间莫里斯水迷宫测试。对于空间部分，在完成为期3天的获取方案后48小时进行一次记忆保留试验（每天8次试验）。诱导IL-1β不影响非空间学习，但与空间任务的习得延迟和保留减少有关。这些行为障碍伴随着强烈的反应性胶质瘤和海马中炎症基因mRNA表达的升高。我们的研究结果表明，延长的神经炎症反应本身可能影响记忆过程，并支持IL-1βXAT转基因小鼠在研究年龄和病理相关认知功能障碍中的慢性神经炎症的未来应用。
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-1β, a pro-inflammatory cytokine upregulated during aging and Alzheimer’s disease, on cognition in mice. We utilized the IL-1βXAT 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-1βXAT 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-1βXAT transgenic mice to investigate chronic neuroinflammation in age- and pathology-related cognitive dysfunction.
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影响因子：
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