Alzheimer's disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4-10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.

译文

阿尔茨海默氏病 (AD) 的特征不仅是认知缺陷和神经病理变化,而且还包括一些可能导致生活质量下降的非认知行为症状。据报道,AD患者的核心体温和身体活动的昼夜节律紊乱,尽管这些变化的原因和后果尚不清楚。因此,我们通过远程无线电遥测表征了雄性三重转基因AD小鼠 (3xTgAD) 和非转基因 (non-Tg) 对照小鼠的体温和活动的昼夜节律模式。在4个月大时,每天的温度节律是阶段性的,到6个月大时,在3xtgad小鼠中观察到平均核心体温和温度节律幅度的增加。在4至9个月大的3xtgad小鼠中,日常活动节律没有差异,但是到10个月大时,检测到3xtgad小鼠的平均日常活动增加和活动曲线的幅度。在所有年龄 (4-10个月),与非Tg小鼠相比,3xtgad小鼠的食物摄入量更高。温度的变化似乎并不仅仅是由于食物摄入量的增加,并且不是环氧合酶依赖性的,因为慢性布洛芬治疗并未消除温度升高。在3xtgad小鼠的下丘脑中未发现 β-淀粉样蛋白 (a β) 斑块或神经原纤维缠结,这是温度调节的关键区域,尽管在10个月大的3xtgad小鼠的海马和杏仁核中观察到这些病理特征。这些数据证明了3xTgAD小鼠的核心体温和活动的年龄依赖性变化,这些变化在明显的AD相关神经病理学之前存在,与在AD患者中观察到的相似。因此,3xtgad小鼠可能是研究AD非认知行为变化所涉及的潜在机制的合适模型。

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