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首页> 外文期刊>Magnetic resonance in medicine: official journal of the Society of Magnetic Resonance in Medicine >Magnetic resonance spectroscopy in vivo of neurochemicals in a transgenic model of Alzheimer's disease: A longitudinal study of metabolites, relaxation time, and behavioral analysis in TASTPM and wild-type mice
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Magnetic resonance spectroscopy in vivo of neurochemicals in a transgenic model of Alzheimer's disease: A longitudinal study of metabolites, relaxation time, and behavioral analysis in TASTPM and wild-type mice

机译：阿尔茨海默氏病转基因模型中神经化学物质的体内磁共振波谱：TASTPM和野生型小鼠体内代谢产物，弛豫时间和行为分析的纵向研究

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摘要

Alzheimer's disease (AD) is the most common form of dementia in the elderly. Due to ongoing advances in our understanding of the underlying pathology of AD, many potential new targets for therapeutics are becoming available. Transgenic mouse models of AD have helped in furthering our understanding of AD and also provide a vehicle for preclinical testing of new, putative disease-modifying therapeutics, which may have potential for translation to use in clinical trials. To identify possible translational biomarkers, we have studied the longitudinal cerebral metabolic pattern of the TASTPM transgenic AD mouse, a double transgenic mouse overexpressing human mutant amyloid precursor protein (hAPP695swe) and presenilin-1 (M146V) by 1H magnetic resonance spectroscopy, along with concurrent brain T1/T2 mapping and behavioral testing. We found significant differences in creatine, glutamate, N-acetylaspartate, choline-containing compounds, and myo-inositol between TASTPM and wild-type mice. In the case of N-acetylaspartate and myo-inositol, there were similarities to differences detected in human AD. T1/T2 values were shorter overall in TASTPM mice, indicating possible differences in water content between TASTPM and wild-type mice. In older TASTPM mice, exploratory behavior became more random, indicating a possible memory deficiency. The decrease in behavioral performance correlated in the transgenic group with higher expression of myo-inositol.
机译：阿尔茨海默氏病（AD）是老年人中最常见的痴呆形式。由于我们对AD的基本病理学的理解不断进步，因此许多潜在的治疗新靶标正变得可用。 AD的转基因小鼠模型有助于加深我们对AD的了解，也为进行新的假定的改善疾病的疗法进行临床前测试提供了一种工具，这种疗法可能具有在临床试验中进行翻译的潜力。为了确定可能的翻译生物标志物，我们通过1H磁共振波谱研究了TASTPM转基因AD小鼠的纵向脑代谢模式，该小鼠是一种过表达人类突变体淀粉样前体蛋白（hAPP695swe）和早老素-1（M146V）的双转基因小鼠，大脑T1 / T2映射和行为测试。我们发现TASTPM和野生型小鼠之间的肌酸，谷氨酸，N-乙酰天门冬氨酸，含胆碱化合物和肌醇存在显着差异。就N-乙酰天门冬氨酸和肌醇而言，与人类AD中检测到的差异相似。 TASTPM小鼠的总体T1 / T2值较短，表明TASTPM和野生型小鼠之间的水含量可能存在差异。在年长的TASTPM小鼠中，探索行为变得更加随机，表明可能存在记忆不足。行为表现的下降在转基因组中与肌醇的更高表达相关。

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