Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice.
Sustained hippocampal IL-1beta overexpression impairs contextual and spatial memory in transgenic mice.
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DOI：
10.1016/j.bbi.2009.10.002
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发表时间：
2010-02
影响因子：
15.1
通讯作者：
O'Banion, M. Kerry
中科院分区：
文献类型：
--
作者：
Hein, Amy M.;Stasko, Melissa R.;Matousek, Sarah B.;Scott-McKean, Jonah J.;Maier, Steven F.;Olschowka, John A.;Costa, Alberto C. S.;O'Banion, M. Kerry
关键词：
神经炎症性疾病，如创伤性脑损伤、衰老、阿尔茨海默病和唐氏综合症，通常与认知功能障碍有关。尽管伴随这些疾病的各种细胞和分子变化模糊了炎症与记忆受损之间的联系，但许多研究都将炎症作为这些缺陷的致病介质。因此，我们使用带有休眠人IL-1β切除激活基因的转基因小鼠模型，通过时间和区域控制来指导IL-1β的过表达。两周的海马IL-1β过表达损害了雄性和雌性小鼠的长期情境和空间记忆，而海马非依赖性和短期记忆保持完整。人IL-1β过表达激活了胶质细胞，升高了小鼠IL-1β蛋白和PGE2水平，并特异性地增加了海马内的促炎细胞因子和趋化因子mrna，而对肝脏中的炎症mrna没有可检测到的影响。持续的神经炎症也降低了可塑性相关基因Arc的基础水平和调节诱导水平。
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-1β excisional activation transgene to direct overexpression of IL-1β with temporal and regional control. Two weeks of hippocampal IL-1β 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-1β overexpression activated glia, elevated murine IL-1β protein and PGE2 levels, and increased proinflammatory 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.
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影响因子：
16.2
作者：
Plath, Niels;Ohana, Ora;Kuhl, Dietmar
通讯作者：
Kuhl, Dietmar
影响因子：
6.1
作者：
Campbell, Sandra J.;Deacon, Rob M. J.;Anthony, Daniel C.
通讯作者：
Anthony, Daniel C.
影响因子：
4.7
作者：
Campbell, Sandra J.;Zahid, Imran;Anthony, Daniel C.
通讯作者：
Anthony, Daniel C.
影响因子：
3.3
作者：
Hein, A. M.;Stutzman, D. L.;Maier, S. F.
通讯作者：
Maier, S. F.
影响因子：
15.1
作者：
GIBERTINI, M;NEWTON, C;KLEIN, TW
通讯作者：
KLEIN, TW