病毒介导的成年中枢神经系统中的基因操作。

Virally mediated gene manipulation in the adult CNS.

机构信息

Department of Neurobiology and Ethology, Center for Gene Manipulation in the Brain (CGMB), University of Haifa Haifa, Israel.

出版信息

Front Mol Neurosci. 2011 Dec 26;4:57. doi: 10.3389/fnmol.2011.00057. eCollection 2011 Oct 5.

Abstract

Understanding how the CNS functions poses one of the greatest challenges in modern life science and medicine. Studying the brain is especially challenging because of its complexity, the heterogeneity of its cellular composition, and the substantial changes it undergoes throughout its life-span. The complexity of adult brain neural networks results also from the diversity of properties and functions of neuronal cells, governed, inter alia, by temporally and spatially differential expression of proteins in mammalian brain cell populations. Hence, research into the biology of CNS activity and its implications to human and animal behavior must use novel scientific tools. One source of such tools is the field of molecular genetics-recently utilized more and more frequently in neuroscience research. Transgenic approaches in general, and gene targeting in rodents have become fundamental tools for elucidating gene function in the CNS. Although spectacular progress has been achieved over recent decades by using these approaches, it is important to note that they face a number of restrictions. One of the main challenges is presented by the temporal and spatial regulation of introduced genetic manipulations. Viral vectors provide an alternative approach to temporally regulated, localized delivery of genetic modifications into neurons. In this review we describe available technologies for gene transfer into the adult mammalian CNS that use both viral and non-viral tools. We discuss viral vectors frequently used in neuroscience, with emphasis on lentiviral vector (LV) systems. We consider adverse effects of LVs, and the use of LVs for temporally and spatially controllable manipulations. Especially, we highlight the significance of viral vector-mediated genetic manipulations in studying learning and memory processes, and how they may be effectively used to separate out the various phases of learning: acquisition, consolidation, retrieval, and maintenance.

摘要

理解中枢神经系统的功能是现代生命科学和医学面临的最大挑战之一。研究大脑尤其具有挑战性,因为它的复杂性、细胞组成的异质性以及它在整个生命周期中经历的巨大变化。成年大脑神经网络的复杂性还源于神经元细胞的特性和功能的多样性,这些特性和功能受到哺乳动物脑细胞群体中蛋白质时空差异表达的调控。因此,研究中枢神经系统活动及其对人类和动物行为的影响必须使用新的科学工具。这些工具的一个来源是分子遗传学领域——最近在神经科学研究中越来越频繁地使用。转基因方法,特别是在啮齿动物中的基因靶向,已成为阐明中枢神经系统中基因功能的基本工具。尽管近几十年来通过使用这些方法取得了引人瞩目的进展,但重要的是要注意到它们面临着许多限制。其中一个主要挑战是引入的遗传操作的时空调节。病毒载体为在神经元中进行时空调节、局部遗传修饰提供了一种替代方法。在这篇综述中,我们描述了用于将基因转移到成年哺乳动物中枢神经系统的现有技术,这些技术使用了病毒和非病毒工具。我们讨论了神经科学中常用的病毒载体,重点介绍了慢病毒载体 (LV) 系统。我们考虑了 LV 的不良反应,以及它们在时间和空间上的可控性操作中的应用。特别是,我们强调了病毒载体介导的遗传操作在研究学习和记忆过程中的重要性,以及它们如何有效地用于分离学习的各个阶段:获取、巩固、检索和维持。

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