Cañete T, Blázquez G, Tobeña A, Giménez-Llort L, Fernández-Teruel A
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.
Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institute of Neurosciences, Autonomous University of Barcelona, 08193 Bellaterra, Barcelona, Spain.
Behav Brain Res. 2015 Mar 15;281:156-71. doi: 10.1016/j.bbr.2014.11.004. Epub 2014 Nov 13.
Alzheimer disease is the most common neurodegenerative disorder and cause of senile dementia. It is characterized by an accelerated memory loss, and alterations of mood, reason, judgment and language. The main neuropathological hallmarks of the disorder are β-amyloid (βA) plaques and neurofibrillary Tau tangles. The triple transgenic 3xTgAD mouse model develops βA and Tau pathologies in a progressive manner which mimicks the pattern that takes place in the human brain with AD, and showing cognitive alterations characteristic of the disease. The present study intended to examine whether 3xTgAD mice of both sexes present cognitive, emotional and other behavioral alterations at the early age of 4 months, an age in which only some intraneuronal amyloid accumulation is found. Neonatal handling (H) is an early-life treatment known to produce profound and long-lasting behavioral and neurobiological effects in rodents, as well as improvements in cognitive functions. Therefore, we also aimed at evaluating the effects of H on the behavioral/cognitive profile of 4-month-old male and female 3xTgAD mice. The results indicate that, (1) 3xTgAD mice present spatial learning/memory deficits and emotional alterations already at the early age of 4 months, (2) there exists sexual dimorphism effects on several behavioral variables at this age, (3) neonatal handling exerts a preventive effect on some cognitive (spatial learning) and emotional alterations appearing in 3xTgAD mice already at early ages, and 4) H treatment appears to produce stronger positive effects in females than in males in several spatial learning measures and in the open field test.
阿尔茨海默病是最常见的神经退行性疾病，也是老年痴呆症的病因。其特征是记忆力加速丧失，以及情绪、推理、判断力和语言能力的改变。该疾病的主要神经病理学特征是β-淀粉样蛋白（βA）斑块和神经原纤维缠结。三转基因3xTgAD小鼠模型以渐进方式发展出βA和Tau病理学特征，模拟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。本研究旨在检查4个月大的幼年两性3xTgAD小鼠是否存在认知、情绪和其他行为改变，这个年龄段仅发现一些神经元内淀粉样蛋白积累。新生期抚摸（H）是一种已知的早期生命期处理方式，可在啮齿动物中产生深刻且持久的行为和神经生物学效应，以及认知功能的改善。因此，我们还旨在评估H对4个月大的雄性和雌性3xTgAD小鼠行为/认知特征的影响。结果表明，（1）3xTgAD小鼠在4个月大的幼年时就已出现空间学习/记忆缺陷和情绪改变，（2）这个年龄段在几个行为变量上存在性别差异效应，（3）新生期抚摸对3xTgAD小鼠早期就已出现的一些认知（空间学习）和情绪改变具有预防作用，（4）在几种空间学习测量和旷场试验中，H处理对雌性产生的积极影响似乎比雄性更强。
