广泛用于阿尔茨海默病(AD)研究的5xFAD转基因小鼠模型概括了许多与AD相关的表型,具有相对较早的发病和积极的年龄依赖性进展。除了在2个月大时与神经炎症一起发展淀粉样肽沉积物,以及在4个月大时表现出神经元衰退,到9个月大时加剧,这些小鼠表现出广泛的行为障碍。在这次审查中,我们提出了5xFAD小鼠行为功能障碍的广泛库,分为四类:运动技能,感觉功能,学习和记忆能力,和神经精神症状.电机问题,与敏捷性和反射运动相关,以及平衡和协调,和骨骼肌功能,通常出现在小鼠达到9个月大的时候。感官功能(如味道,气味,听力,和视力)当淀粉样肽积聚和神经炎症扩散到相关的解剖结构时开始恶化。认知功能,包括学习和记忆能力,比如视觉识别,联想,空间工作,参考学习,从4到6个月的年龄,记忆力表现出下降的迹象。关于神经精神样症状,包括冷漠,焦虑和抑郁,以及探索行为的意愿,人们认为,动机的变化出现在大约6个月的年龄。不幸的是,来自不同实验室的许多研究在得出的结论和发病年龄的确定上往往是矛盾的,在啮齿动物模型中进行临床前研究不容易转化为人类。这种变异性可能是由于一系列与动物本身相关的因素,住房和畜牧业条件,和实验设置。在即将进行的研究中,在5xFAD转基因小鼠中进行行为测试时,实验细节更加清晰,可以最大限度地减少不一致,并确保结果的可靠性和可重复性.
The 5xFAD transgenic mouse model widely used in Alzheimer\'s disease (AD) research recapitulates many AD-related phenotypes with a relatively early onset and aggressive age-dependent progression. Besides developing amyloid peptide deposits alongside neuroinflammation by the age of 2 months, as well as exhibiting neuronal decline by the age of 4 months that intensifies by the age of 9 months, these mice manifest a broad spectrum of behavioural impairments. In this review, we present the extensive repertoire of behavioural dysfunctions in 5xFAD mice, organised into four categories: motor skills, sensory function, learning and memory abilities, and neuropsychiatric-like symptoms. The motor problems, associated with agility and reflex movements, as well as balance and coordination, and skeletal muscle function, typically arise by the time mice reach 9 months of age. The sensory function (such as taste, smell, hearing, and vision) starts to deteriorate when amyloid peptide buildups and neuroinflammation spread into related anatomical structures. The cognitive functions, encompassing learning and memory abilities, such as visual recognition, associative, spatial working, reference learning, and memory show signs of decline from 4 to 6 months of age. Concerning neuropsychiatric-like symptoms, comprising apathy, anxiety and depression, and the willingness for exploratory behaviour, it is believed that motivational changes emerge by approximately 6 months of age. Unfortunately, numerous studies from different laboratories are often contradictory on the conclusions drawn and the identification of onset age, making preclinical studies in rodent models not easily translatable to humans. This variability is likely due to a range of factors associated with animals themselves, housing and husbandry conditions, and experimental settings. In the forthcoming studies, greater clarity in experimental details when conducting behavioural testing in 5xFAD transgenic mice could minimise the inconsistencies and could ensure the reliability and the reproducibility of the results.