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[阿尔茨海默病转基因小鼠模型(3xTg-AD)中与先天行为任务相关的海马区形态学分析]

[Morphological analysis of the hippocampal region associated with an innate behaviour task in the transgenic mouse model (3xTg-AD) for Alzheimer disease].

作者信息

Orta-Salazar E, Feria-Velasco A, Medina-Aguirre G I, Díaz-Cintra S

机构信息

Centro Universitario de Ciencias Biológicas y Agropecuarias. Universidad de Guadalajara, Zapopan, Jalisco, México.

出版信息

Neurologia. 2013 Oct;28(8):497-502. doi: 10.1016/j.nrl.2013.01.014. Epub 2013 Aug 23.

Abstract

INTRODUCTION

Different animal models for Alzheimer disease (AD) have been designed to support the hypothesis that the neurodegeneration (loss of neurons and synapses with reactive gliosis) associated with Aβ and tau deposition in these models is similar to that in the human brain. These alterations produce functional changes beginning with decreased ability to carry out daily and social life activities, memory loss, and neuropsychiatric disorders in general. Neuronal alteration plays an important role in early stages of the disease, especially in the CA1 area of hippocampus in both human and animal models.

METHODS

Two groups (WT and 3xTg-AD) of 11-month-old female mice were used in a behavioural analysis (nest building) and a morphometric analysis of the CA1 region of the dorsal hippocampus.

RESULTS

The 3xTg-AD mice showed a 50% reduction in nest quality associated with a significant increase in damaged neurons in the CA1 hippocampal area (26%±6%, P<.05) compared to the WT group.

CONCLUSIONS

The decreased ability to carry out activities of daily living (humans) or nest building (3xTg-AD mice) is related to the neuronal alterations observed in AD. These alterations are controlled by the hippocampus. Post-mortem analyses of the human hippocampus, and the CA1 region in 3xTg-AD mice, show that these areas are associated with alterations in the deposition of Aβ and tau proteins, which start accumulating in the early stages of AD.

摘要

引言

已经设计了不同的阿尔茨海默病(AD)动物模型,以支持这样的假说,即这些模型中与Aβ和tau沉积相关的神经退行性变(神经元和突触丧失伴反应性胶质细胞增生)与人类大脑中的情况相似。这些改变会引发功能变化,最初表现为进行日常生活和社交活动的能力下降、记忆力丧失以及一般的神经精神障碍。神经元改变在疾病早期阶段起着重要作用,尤其是在人类和动物模型的海马体CA1区域。

方法

使用两组11月龄雌性小鼠(野生型和3xTg-AD)进行行为分析(筑巢)以及对背侧海马体CA1区域的形态计量分析。

结果

与野生型组相比,3xTg-AD小鼠的筑巢质量降低了50%,同时海马体CA1区域受损神经元显著增加(26%±6%,P<.05)。

结论

进行日常生活活动(人类)或筑巢(3xTg-AD小鼠)的能力下降与AD中观察到的神经元改变有关。这些改变受海马体控制。对人类海马体以及3xTg-AD小鼠的CA1区域进行的尸检分析表明,这些区域与Aβ和tau蛋白沉积的改变有关,这些蛋白在AD早期阶段就开始积累。

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