Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice
Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice
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DOI：
10.1016/j.brainres.2005.08.004
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发表时间：
2005-10-12
期刊：
影响因子：
2.9
通讯作者：
Fujiwara, M
中科院分区：
文献类型：
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作者：
Egashira, N;Iwasaki, K;Fujiwara, M
突变型R406 W人类tau最初在与染色体17（FTDP-17）相关的额颞叶痴呆和帕金森综合征中被鉴定，并引起临床上类似于阿尔茨海默病（AD）的遗传性tau蛋白病。在当前的研究中，我们检查了R406 W转基因（Tg）小鼠在强迫游泳试验中的表现，该试验对人类抑郁症的抗抑郁疗效具有较高的预测性，并发现不动时间的增加。相反，R406 W Tg小鼠的运动功能和焦虑相关的情绪反应正常。此外，选择性5-羟色胺再摄取抑制剂（SSR 1），氟伏沙明（100 mg/ka，p.o.），显着减少这种增强的不动时间，而去甲肾上腺素再摄取抑制剂，地昔帕明，没有效果。在体内微透析研究中，R406 W Tg小鼠额叶皮质细胞外5-羟基吲哚乙酸（5-HIAA）水平显著降低，并且细胞外5-羟色胺（5-HT）水平也有降低的趋势。此外，氟伏沙明，减少不动时间的增强，显着增加细胞外5-HT水平在R406 W Tg小鼠。这些结果提示R406 W转基因小鼠表现出涉及多巴胺能神经元的抑郁相关行为改变，为研究AD伴抑郁提供了动物模型。(c)2005 Elsevier B.V保留所有权利。
Mutant R406W human tau was originally identified in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and causes a hereditary tauopathy that clinically resembles Alzheimer's disease (AD). In the current study, we examined the performance of R406W transgenic (Tg) mice in the forced swimming test, a test with high predictivity of antidepressant efficacy in human depression, and found an enhancement of the immobility time. In contrast, the motor function and anxiety-related emotional response of R406W Tg mice were normal. Furthermore, a selective serotonin reuptake inhibitor (SSR1), fluvoxamine (100 mg/ka, p.o.), significantly reduced this enhancement of the immobility time, whereas a noradrenaline reuptake inhibitor, desipramine, had no effect. In an in vivo microdialysis study, R406W Tg mice exhibited a significantly decreased extracellular 5-hydroxyindoleacetic acid (5-HIAA) level in the frontal cortex and also exhibited a tendency toward a decreased extracellular 5-hydroxytryptamine (5-HT) level. Moreover, fluvoxamine, which reduced the enhancement of the immobility time, significantly increased the extracellular 5-HT level in R406W Tg mice. These results suggest that R406W Tg mice exhibit changes in depress ion-related behavior involving serotonergic neurons and provide an animal model for investigating AD with depression. (c) 2005 Elsevier B.V All rights reserved.