Longitudinal investigation of neuroinflammation and metabolite profiles in the APP(swe) ×PS1(Δe9) transgenic mouse model of Alzheimer's disease.
Longitudinal investigation of neuroinflammation and metabolite profiles in the APP(swe) ×PS1(Δe9) transgenic mouse model of Alzheimer's disease.
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DOI：
10.1111/jnc.14251
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发表时间：
2018-03
影响因子：
4.7
通讯作者：
Boutin H
中科院分区：
文献类型：
--
作者：
Chaney A;Bauer M;Bochicchio D;Smigova A;Kassiou M;Davies KE;Williams SR;Boutin H
越来越多的证据表明，神经炎与包括阿尔茨海默病(AD)在内的许多神经系统疾病有关；然而，它对疾病表现和/或进展的确切贡献却知之甚少。因此，有必要对健康和疾病中的神经炎症进行研究。在这里，我们研究了APP SWE×PS1ΔE9转基因小鼠AD模型的认知功能下降、神经炎症和其他病理生理变化。将转基因(TG)小鼠与C57BL/6野生型(WT)小鼠在6、12和18月龄时进行比较。用~(18)F]DPA-714正电子发射断层扫描和~1H磁共振波谱(MRS)测定肌醇水平。通过观察N-乙酰天冬氨酸(NAA)、含有胆碱的化合物、牛磺酸和谷氨酸来研究神经元和细胞功能障碍，也使用MRS观察到认知功能下降通过工作记忆测试在12岁时首次在TG小鼠中观察到。与年龄匹配的WT鼠和6岁的TG鼠相比，18岁的TG鼠的海马区和皮质中的[18F]DPA-714摄取显著增加。没有看到基因对代谢物水平的总体影响；然而，与WT相比，18岁的TG小鼠的NAA水平显著降低。此外，随着年龄的增长，谷氨酸水平下降，胆碱水平上升。因此，我们可以得出结论，在TG动物中观察到神经炎症和认知能力下降的增加，而随着年龄增长发生的NAA改变在TG小鼠中加剧。这些结果支持神经炎症和代谢物改变在AD和衰老中的作用。
There is increasing evidence linking neuroinflammation to many neurological disorders including Alzheimer's disease (AD); however, its exact contribution to disease manifestation and/or progression is poorly understood. Therefore, there is a need to investigate neuroinflammation in both health and disease. Here, we investigate cognitive decline, neuroinflammatory and other pathophysiological changes in the APP swe×PS1Δe9 transgenic mouse model of AD. Transgenic (TG) mice were compared to C57BL/6 wild type (WT) mice at 6, 12 and 18 months of age. Neuroinflammation was investigated by [18F]DPA‐714 positron emission tomography and myo‐inositol levels using 1H magnetic resonance spectroscopy (MRS) in vivo. Neuronal and cellular dysfunction was investigated by looking at N‐acetylaspartate (NAA), choline‐containing compounds, taurine and glutamate also using MRS. Cognitive decline was first observed at 12 m of age in the TG mice as assessed by working memory tests . A significant increase in [18F]DPA‐714 uptake was seen in the hippocampus and cortex of 18 m‐old TG mice when compared to age‐matched WT mice and 6 m‐old TG mice. No overall effect of gene was seen on metabolite levels; however, a significant reduction in NAA was observed in 18 m‐old TG mice when compared to WT. In addition, age resulted in a decrease in glutamate and an increase in choline levels. Therefore, we can conclude that increased neuroinflammation and cognitive decline are observed in TG animals, whereas NAA alterations occurring with age are exacerbated in the TG mice. These results support the role of neuroinflammation and metabolite alteration in AD and in ageing.
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影响因子：
16.6
作者：
Daniels MJ;Rivers-Auty J;Schilling T;Spencer NG;Watremez W;Fasolino V;Booth SJ;White CS;Baldwin AG;Freeman S;Wong R;Latta C;Yu S;Jackson J;Fischer N;Koziel V;Pillot T;Bagnall J;Allan SM;Paszek P;Galea J;Harte MK;Eder C;Lawrence CB;Brough D
通讯作者：
Brough D
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J
影响因子：
3.3
作者：
GRUETTER, R
通讯作者：
GRUETTER, R
APP/PS1转基因小鼠大脑代谢物和认知功能与年龄相关的变化
影响因子：
2.7
作者：
Chen, Shuang-qing;Cai, Qing;Zang, Feng-chao
通讯作者：
Zang, Feng-chao
影响因子：
14.5
作者：
Hamelin, Lorraine;Lagarde, Julien;Sarazin, Marie
通讯作者：
Sarazin, Marie