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在阿尔茨海默病病理的生命末期小鼠中,后凸和奇异模式会损害自发步态表现,而在正常衰老中步态则得以保留。

Kyphosis and bizarre patterns impair spontaneous gait performance in end-of-life mice with Alzheimer's disease pathology while gait is preserved in normal aging.

机构信息

Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.

出版信息

Neurosci Lett. 2022 Jan 10;767:136280. doi: 10.1016/j.neulet.2021.136280. Epub 2021 Sep 30.

Abstract

The shorter life spans of mice provide an exceptional experimental gerontology scenario. We previously described increased bizarre (disruptive) behaviors in the 6-month-old 3xTg-AD mice model for Alzheimer's disease (AD), compared to C57BL/6J wildtype (NTg), when confronting new environments. In the present work, we evaluated spontaneous gait and exploratory activity at old age, using 16-month-old mice. Male sex was chosen since sex-dependent psychomotor effects of aging are stronger in NTg males than females and, at this age, male 3 × Tg-AD mice are close to an end-of-life status due to increased mortality rates. Mice's behavior was evaluated in a transparent test box during the neophobia response. Stretching, jumping, backward movements and bizarre circling were identified during the gait and exploratory activity. The results corroborate that in the face of novelty and recognition of places, old 3xTg-AD mice exhibit increased bizarre behaviors than mice with normal aging. Furthermore, bizarre circling and backward movements delayed the elicitation of locomotion and exploration, in an already frail scenario, as shown by highly prevalent kyphosis in both groups. Thus, the translational study of co-occurrence of psychomotor impairments and anxiety-like behaviors can be helpful for understanding and managing the progressive functional deterioration shown in aging, especially in AD.

摘要

寿命较短的老鼠为实验性老年学提供了一个特殊的场景。我们之前描述过,与 C57BL/6J 野生型(NTg)相比,阿尔茨海默病(AD)的 3xTg-AD 小鼠模型在 6 个月大时,面对新环境会出现更多的奇异(破坏)行为。在本研究中,我们在老年时使用 16 个月大的小鼠评估了自发步态和探索活动。选择雄性是因为在 NTg 雄性中,衰老的性动力心理影响比雌性更强,而且在这个年龄,雄性 3xTg-AD 小鼠由于死亡率增加,已经接近生命末期。在新异反应期间,在透明测试箱中评估了小鼠的行为。在步态和探索活动期间,确定了伸展、跳跃、后退运动和奇异的盘旋。结果证实,在面对新奇事物和识别地点时,年老的 3xTg-AD 小鼠比正常衰老的小鼠表现出更多的奇异行为。此外,奇异的盘旋和后退运动延迟了运动和探索的诱发,在已经脆弱的情况下,两组都普遍存在脊柱后凸。因此,对运动和焦虑样行为共病的转化研究有助于理解和管理衰老过程中表现出的进行性功能恶化,特别是在 AD 中。

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