Loss of APP in mice increases thigmotaxis and is associated with elevated brain expression of IL-13 and IP-10/CXCL10.
Loss of APP in mice increases thigmotaxis and is associated with elevated brain expression of IL-13 and IP-10/CXCL10.
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DOI：
10.1016/j.physbeh.2021.113533
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发表时间：
2021-10-15
影响因子：
2.9
通讯作者：
Soriano, Salvador
中科院分区：
文献类型：
--
作者：
Mayagoitia, Karina;Tolan, Andrew J.;Shammi, Shohali;Shin, Samuel D.;Menchaca, Jesus A.;Figueroa, Johnny D.;Wilson, Christopher G.;Bellinger, Denise L.;Ahmed, Abu Shufian Ishtiaq;Soriano, Salvador
阿尔茨海默病（AD）是一种进行性神经退行性疾病，会导致记忆丧失，并经常伴有焦虑加剧。虽然阿尔茨海默病是一种异质性疾病，但炎症通路失调是一种一致的事件。有趣的是，淀粉样蛋白前体蛋白（APP）是淀粉样蛋白肽Aβ的来源，也是有效调节先天免疫反应所必需的。在这里，我们假设小鼠APP功能的丧失会导致认知丧失和焦虑行为，这两种行为都是AD的典型特征，同时炎症介质的表达也会发生变化。为了验证这一假设，我们对12 - 18周龄的雄性和雌性野生型和AppKO小鼠进行了开放场、y迷宫和新物体识别测试，以测量其运动性、短期空间记忆和长期识别记忆。然后，我们进行了定量多重免疫分析，以测量与AD和焦虑相关的32种细胞因子/趋化因子的水平。我们的研究结果表明，与野生型对照相比，AppKO小鼠的移行行为增加，但没有记忆障碍，这种表型与IP-10和IL-13水平升高相关。未来的研究将确定这些炎症介质的失调是否与AD的发病机制有关。
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that leads to memory loss and is often accompanied by increased anxiety. Although AD is a heterogeneous disease, dysregulation of inflammatory pathways is a consistent event. Interestingly, the amyloid precursor protein (APP), which is the source of the amyloid peptide Aβ, is also necessary for the efficient regulation of the innate immune response. Here, we hypothesize that loss of APP function in mice would lead to cognitive loss and anxiety behavior, both of which are typically present in AD, as well as changes in the expression of inflammatory mediators. To test this hypothesis, we performed open field, Y-maze and novel object recognition tests on 12–18-week-old male and female wildtype and AppKO mice to measure thigmotaxis, short-term spatial memory and long-term recognition memory. We then performed a quantitative multiplexed immunoassay to measure levels of 32 cytokines/chemokines associated with AD and anxiety. Our results showed that AppKO mice, compared to wildtype controls, experienced increased thigmotactic behavior but no memory impairments, and this phenotype correlated with increased IP-10 and IL-13 levels. Future studies will determine whether dysregulation of these inflammatory mediators contributes to pathogenesis in AD.
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影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
影响因子：
64.5
作者：
Duce JA;Tsatsanis A;Cater MA;James SA;Robb E;Wikhe K;Leong SL;Perez K;Johanssen T;Greenough MA;Cho HH;Galatis D;Moir RD;Masters CL;McLean C;Tanzi RE;Cappai R;Barnham KJ;Ciccotosto GD;Rogers JT;Bush AI
通讯作者：
Bush AI
影响因子：
1.3
作者：
Leppänen, PK;Ravaja, N;Ewalds-Kvist, SBM
通讯作者：
Ewalds-Kvist, SBM
影响因子：
6.1
作者：
Nunes, Ana;Pressey, Sarah N. R.;Soriano, Salvador
通讯作者：
Soriano, Salvador
影响因子：
1.7
作者：
Bluthé, RM;Bristow, A;Dantzer, R
通讯作者：
Dantzer, R