Giménez-Llort Lydia, Marin-Pardo Daniela, Marazuela Paula, Hernández-Guillamón Mar
Institut de Neurociències, Universitat Autònoma de Barcelona, E-08193 Barcelona, Spain.
Department of Psychiatry and Forensic Medicine, School of Medicine, Universitat Autònoma de Barcelona, E-08193 Barcelona, Spain.
Biomedicines. 2021 Jun 2;9(6):636. doi: 10.3390/biomedicines9060636.
New evidence refers to a high degree of heterogeneity in normal but also Alzheimer's disease (AD) clinical and temporal patterns, increased mortality, and the need to find specific end-of-life prognosticators. This heterogeneity is scarcely explored in very old male AD mice models due to their reduced survival. In the present work, using 915 (432 APP23 and 483 C57BL/6 littermates) mice, we confirmed the better survival curves in male than female APP23 mice and respective wildtypes, providing the chance to characterize behavioral signatures in middle-aged, old, and long-lived male animals. The sensitivity of a battery of seven paradigms for comprehensive screening of motor (activity and gait analysis), neuropsychiatric and cognitive symptoms was analyzed using a cohort of 56 animals, composed of 12-, 18- and 24-month-old male APP23 mice and wildtype littermates. Most variables analyzed detected age-related differences. However, variables related to coping with stress, thigmotaxis, frailty, gait, and poor cognition better discriminated the behavioral phenotype of male APP23 mice through the three old ages compared with controls. Most importantly, non-linear age- and genotype-dependent behavioral signatures were found in long-lived animals, suggesting crosstalk between chronological and biological/behavioral ages useful to study underlying mechanisms and distinct compensations through physiological and AD-associated aging.
新证据表明，正常及阿尔茨海默病（AD）的临床和时间模式存在高度异质性，死亡率增加，且需要找到特定的临终预后指标。由于存活期缩短，这种异质性在非常老龄的雄性AD小鼠模型中几乎未得到探究。在本研究中，我们使用了915只小鼠（432只APP23小鼠和483只C57BL/6同窝小鼠），证实了雄性APP23小鼠及其相应野生型的存活曲线优于雌性，这为表征中年、老年和长寿雄性动物的行为特征提供了机会。使用由12、18和24月龄雄性APP23小鼠及其野生型同窝小鼠组成的56只动物队列，分析了一组用于全面筛查运动（活动和步态分析）、神经精神和认知症状的七种范式的敏感性。分析的大多数变量都检测到了与年龄相关的差异。然而，与应对压力、趋触性、虚弱、步态和认知能力差相关的变量，与对照组相比，在三个老龄阶段能更好地区分雄性APP23小鼠的行为表型。最重要的是，在长寿动物中发现了非线性的年龄和基因型依赖性行为特征，这表明时间年龄与生物学/行为年龄之间存在相互作用，有助于研究潜在机制以及通过生理和AD相关衰老的不同补偿机制。
