The effects of MyD88 deficiency on exploratory activity, anxiety, motor coordination, and spatial learning in C57BL/6 and APPswe/PS1dE9 mice.
The effects of MyD88 deficiency on exploratory activity, anxiety, motor coordination, and spatial learning in C57BL/6 and APPswe/PS1dE9 mice.
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DOI：
10.1016/j.bbr.2011.10.027
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发表时间：
2012-02-01
影响因子：
2.7
通讯作者：
Fukuchi, Ken-ichiro
中科院分区：
文献类型：
--
作者：
Lim, Jeong-Eun;Song, Min;Jin, Jingji;Kou, Jinghong;Pattanayak, Abhinandan;Lalonde, Robert;Fukuchi, Ken-ichiro
Toll样受体（TLR）是先天免疫中的模式识别受体家族，并且提供针对病原体和组织损伤的第一线防御。除了在感染、炎症和免疫疾病中发挥重要作用外，最近的研究表明TLR信号传导还参与学习、记忆、情绪和神经发生的调节。由于MyD 88对于除了TLR 3之外的所有TLR的下游信号传导是必需的，因此我们研究了MyD 88缺陷（MyD 88-/-）对小鼠行为功能的影响。此外，我们最近证明，与MyD 88充足的AD小鼠模型相比，MyD 88缺陷的阿尔茨海默病（AD）小鼠模型的脑中Aβ沉积物和可溶性Aβ减少。由于假设Aβ在脑中的蓄积是导致AD认知缺陷的因果事件，因此我们研究了MyD 88缺陷对10月龄AD小鼠模型行为功能的影响。MyD 88缺陷小鼠在高架十字迷宫中表现出更多的焦虑。在运动协调测试中，MyD 88缺陷小鼠在横梁和横杆上停留的时间更长，但在横杆上的初始运动较慢。在Morris水迷宫测试中，MyD 88缺陷似乎改善了空间学习，而与转基因无关。我们的研究结果表明，MyD 88依赖性通路有助于AD小鼠模型及其对照组的行为功能。
Toll-like receptors (TLRs) are a family of pattern-recognition receptors in innate immunity and provide a first line defense against pathogens and tissue injuries. In addition to important roles in infection, inflammation, and immune diseases, recent studies show that TLR signaling is involved in modulation of learning, memory, mood, and neurogenesis. Because MyD88 is essential for the downstream signaling of all TLRs, except TLR3, we investigated the effects of MyD88 deficiency (MyD88-/-) on behavioral functions in mice. Additionally, we recently demonstrated that a mouse model of Alzheimer’s disease (AD) deficient for MyD88 had decreases in Aβ deposits and soluble Aβ in the brain as compared with MyD88 sufficient AD mouse models. Because accumulation of Aβ in the brain is postulated to be a causal event leading to cognitive deficits in AD, we investigated the effects of MyD88 deficiency on behavioral functions in the AD mouse model at 10 months of age. MyD88 deficient mice showed more anxiety in the elevated plus-maze. In the motor coordination tests, MyD88 deficient mice remained on a beam and a bar for a longer time, but with slower initial movement on the bar. In the Morris water maze test, MyD88 deficiency appeared to improve spatial learning irrespective of the transgene. Our findings suggest that the MyD88-dependent pathway contributes to behavioral functions in an AD mouse model and its control group.
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影响因子：
2.5
作者：
Koo JW;Duman RS
通讯作者：
Duman RS
影响因子：
2.7
作者：
File, SE
通讯作者：
File, SE
DOI：
10.1073/pnas.2234031100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Ekdahl, CT;Claasen, JH;Lindvall, O
通讯作者：
Lindvall, O
影响因子：
2.5
作者：
Lalonde, R;Kim, HD;Fukuchi, K
通讯作者：
Fukuchi, K
影响因子：
6
作者：
Doi, Yukiko;Mizuno, Tetsuya;Suzumura, Akio
通讯作者：
Suzumura, Akio