Blázquez Gloria, Cañete Toni, Tobeña Adolf, Giménez-Llort Lydia, Fernández-Teruel Alberto
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neuroscience, Autonomous University of Barcelona, 08193 Bellaterra, Spain.
Behav Brain Res. 2014 Jul 15;268:185-201. doi: 10.1016/j.bbr.2014.04.008. Epub 2014 Apr 15.
Alzheimer's disease is a neurodegenerative disorder associated with age which represents the most common cause of dementia. It is characterized by an accelerated memory loss compared to normal aging, and deterioration of other cognitive abilities that interfere with mood, reason, judgment and language. The main neuropathological hallmarks of the disorder are β-amyloid (βA) plaques and neurofibrillary Tau tangles. Triple transgenic 3×TgAD mouse model develops βA and Tau pathologies in a progressive manner, with a specific temporal and anatomic profile mimicking the pattern that takes place in the human brain with AD, and showing cognitive alterations characteristic of the disease. Environmental enrichment treatment in mice induces behavioral and emotional reactivity changes, including cognitive improvements in some AD-related transgenic mice. The present work intended to characterize the behavioral profile of 3×TgAD mice at advanced stages of neuropathological development (12 and 15 months of age) and to investigate whether environmental enrichment administered during adulthood was able to modify some of their behavioral and cognitive alterations. Results show that, at advanced stages of the disease 3×TgAD mice show deficits of spatial learning acquisition, as well as short-term and working memory deficits, while displaying increased levels of anxiety/fearfulness and normal sensorimotor functions. 3×TgAD mice also show sexual dimorphism, as reflected by increased cognitive deficits in females and increased levels of novelty-induced behavioral inhibition in males. Environmental enrichment exerts some slight positive effects, by mainly improving the initial acquisition of the spatial learning and working memory in 12-month-old 3×TgAD mice. Such effects vary depending on the gender.
阿尔茨海默病是一种与年龄相关的神经退行性疾病，是痴呆最常见的病因。其特征是与正常衰老相比，记忆丧失加速，以及其他认知能力衰退，这些衰退会影响情绪、推理、判断和语言。该疾病主要的神经病理学特征是β-淀粉样蛋白（βA）斑块和神经原纤维缠结。三转基因3×TgAD小鼠模型会逐渐出现βA和Tau病变，其特定的时间和解剖特征模仿了人类大脑中阿尔茨海默病发生的模式，并表现出该疾病特有的认知改变。对小鼠进行环境丰富化处理会引起行为和情绪反应的变化，包括在一些与阿尔茨海默病相关的转基因小鼠中认知能力的改善。本研究旨在描述3×TgAD小鼠在神经病理学发展晚期（12和15月龄）的行为特征，并研究成年期给予环境丰富化处理是否能够改变它们的一些行为和认知改变。结果显示，在疾病晚期，3×TgAD小鼠表现出空间学习获取能力缺陷，以及短期和工作记忆缺陷，但焦虑/恐惧水平增加且感觉运动功能正常。3×TgAD小鼠还表现出性别差异，表现为雌性认知缺陷增加而雄性新奇诱导行为抑制水平增加。环境丰富化处理产生了一些轻微的积极影响，主要表现为改善了12月龄3×TgAD小鼠空间学习和工作记忆的初始获取能力。这些影响因性别而异。
