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阿尔茨海默病小鼠模型中的神经发生

Neurogenesis in mouse models of Alzheimer's disease.

作者信息

Chuang Tsu Tshen

机构信息

Stem Cells DPU, GlaxoSmithKline, 200 Technology Square, Suite 300, Cambridge, MA 01139, USA.

出版信息

Biochim Biophys Acta. 2010 Oct;1802(10):872-80. doi: 10.1016/j.bbadis.2009.12.008. Epub 2010 Jan 6.

Abstract

The brains of the adult mouse and human possess neural stem cells (NSCs) that retain the capacity to generate new neurons through the process of neurogenesis. They share the same anatomical locations of stem cell niches in the brain, as well as the prominent feature of rostral migratory stream formed by neuroblasts migrating from the lateral ventricles towards the olfactory bulb. Therefore the mouse possesses some fundamental features that may qualify it as a relevant model for adult human neurogenesis. Adult born young hippocampal neurons in the mouse display the unique property of enhanced plasticity, and can integrate physically and functionally into existing neural circuits in the brain. Such crucial properties of neurogenesis may at least partially underlie the improved learning and memory functions observed in the mouse when hippocampal neurogenesis is augmented, leading to the suggestion that neurogenesis induction may be a novel therapeutic approach for diseases with cognitive impairments such as Alzheimer's disease (AD). Research towards this goal has benefited significantly from the use of AD mouse models to facilitate the understanding in the impact of AD pathology on neurogenesis. The present article reviews the growing body of controversial data on altered neurogenesis in mouse models of AD and attempts to assess their relative relevance to humans.

摘要

成年小鼠和人类的大脑拥有神经干细胞(NSCs),这些神经干细胞能够通过神经发生过程产生新的神经元。它们在大脑中具有相同的干细胞龛的解剖位置,以及由从侧脑室向嗅球迁移的神经母细胞形成的吻侧迁移流这一显著特征。因此,小鼠具有一些基本特征,这可能使其成为成年人类神经发生的相关模型。小鼠中成年新生的年轻海马神经元具有增强可塑性的独特特性,并且能够在物理和功能上整合到大脑中现有的神经回路中。神经发生的这些关键特性可能至少部分地解释了在增强海马神经发生时小鼠中观察到的学习和记忆功能改善的原因,这表明诱导神经发生可能是治疗诸如阿尔茨海默病(AD)等认知障碍疾病的一种新的治疗方法。朝着这一目标的研究从使用AD小鼠模型中受益匪浅,这有助于理解AD病理对神经发生的影响。本文综述了关于AD小鼠模型中神经发生改变的越来越多的有争议的数据,并试图评估它们与人类的相对相关性。

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