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器官型培养作为测试化学物质对神经系统长期影响的工具。

Organotypic cultures as tool to test long-term effects of chemicals on the nervous system.

机构信息

Departamento de Farmacobiología, México D.F., México.

出版信息

Curr Med Chem. 2010;17(10):987-1001. doi: 10.2174/092986710790820679.

Abstract

The study of neuroscience has vastly benefited from the use of brain slices. This preparation has been fundamental for the understanding of the cellular basis of nervous system function as well as for the study of the mechanisms involved in neuronal network dysfunction. This experimental model provides flexible access, and control of, specific neural circuits and maintains their basic properties, allowing them to reproduce most of their natural network activities. Brain slices permit the combination of sophisticated techniques such as electrophysiology, fluorescence imaging, pharmacology, molecular biology, etc. More recently, the development of organotypic brain slice cultures has expanded the use of modern technical approaches to the study neuronal networks, while increasing their possibilities of evaluating long-term effects of acute experimental conditions, as well as the effects of chronic treatments on neuronal network function in vitro. Here, I will provide an overview of the use of organotypic cultures to understand neuronal network function and dysfunction, as well as the pharmacological approaches used for these studies. As a final example, I will review the studies performed in organotypic cultures regarding the deleterious effects of long-term amyloid beta application on neuronal networks in vitro, as well as the use of drugs that may prevent or revert their deleterious effects on nervous system function. Overall, this review will provide elements to support the use of organotypic cultures as a very reliable model to explore long-term neuropharmacological studies in vitro.

摘要

神经科学的研究极大地受益于脑片的使用。这种制备方法对于理解神经系统功能的细胞基础以及研究神经元网络功能障碍所涉及的机制至关重要。这种实验模型提供了对特定神经回路的灵活访问和控制,并保持其基本特性,使它们能够再现大部分自然网络活动。脑片允许结合电生理学、荧光成像、药理学、分子生物学等复杂技术。最近,器官型脑片培养的发展扩大了现代技术方法在研究神经元网络中的应用,同时增加了评估急性实验条件的长期影响以及慢性处理对体外神经元网络功能的影响的可能性。在这里,我将概述器官型培养在理解神经元网络功能和功能障碍以及用于这些研究的药理学方法中的应用。作为最后一个例子,我将回顾在器官型培养中进行的关于长期淀粉样蛋白β应用对体外神经元网络的有害影响的研究,以及使用可能预防或逆转其对神经系统功能的有害影响的药物。总的来说,这篇综述将提供支持使用器官型培养作为一种非常可靠的模型来探索体外长期神经药理学研究的元素。

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