Departments of Psychology and Neuroscience, Halifax, Nova Scotia, B3H 4R2, Canada.
Departments of Physiology and Biophysics, Halifax, Nova Scotia, B3H 4R2, Canada; Departments of Obstetrics and Gynecology, Dalhousie University, Halifax, Nova Scotia, B3H 4R2, Canada.
Behav Brain Res. 2021 May 21;406:113214. doi: 10.1016/j.bbr.2021.113214. Epub 2021 Mar 4.
In addition to cognitive decline, patients with Alzheimer's disease (AD) exhibit sensory, motor, and neuropsychiatric deficits. Many AD patients also show weight loss, suggesting that AD may involve a metabolic syndrome. The 5xFAD mouse model shows age-related weight loss compared to wildtype controls, and thus may exhibit metabolic dysfunction. This longitudinal study measured age-related weight loss in female 5xFAD and B6SJL/JF2 wild-type mice from 3 to 12 months of age, and examines some of the behavioural and physiological phenotypes in these mice that have been proposed to contribute to this weight loss. Because some mice had to be singly housed during the study, we also examined genotype by housing interactions. The 5xFAD mice weighed less and ate less than WT littermates starting at 6 months of age, exhibited less home cage activity, had higher frailty scores, less white adipose tissue, and lower leptin expression. At 9 and 12 months of age, heavier 5xFAD mice performed better on the rotarod, suggesting that metabolic deficits which begin between 6 and 9 months of age may exacerbate the behavioural deficits in 5xFAD mice. These results indicate that the 5xFAD mouse is a useful model to study the behavioural and metabolic changes in AD.
除了认知能力下降，阿尔茨海默病（AD）患者还表现出感觉、运动和神经精神缺陷。许多 AD 患者还表现出体重减轻，这表明 AD 可能涉及代谢综合征。5xFAD 小鼠模型与野生型对照相比表现出与年龄相关的体重减轻，因此可能表现出代谢功能障碍。这项纵向研究测量了从 3 到 12 个月大的雌性 5xFAD 和 B6SJL/JF2 野生型小鼠的与年龄相关的体重减轻，并检查了这些小鼠中一些被认为导致体重减轻的行为和生理表型。由于在研究过程中有些小鼠必须单独饲养，我们还检查了饲养方式对基因型的相互作用。从 6 个月大开始，5xFAD 小鼠的体重和摄食量均低于 WT 同窝仔鼠，其笼内活动较少，脆弱性评分较高，白色脂肪组织较少，瘦素表达水平较低。在 9 个月和 12 个月大时，体重较重的 5xFAD 小鼠在旋转棒上的表现更好，这表明 6 至 9 个月之间出现的代谢缺陷可能会加剧 5xFAD 小鼠的行为缺陷。这些结果表明，5xFAD 小鼠是研究 AD 中行为和代谢变化的有用模型。
