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选择性神经毒素——探索大脑的化学工具:最初三十年及以后

Selective neurotoxins, chemical tools to probe the mind: the first thirty years and beyond.

作者信息

Kostrzewa R M

机构信息

Department of Pharmacology, Quillen College of Medicine and Neuroscience Consortium of Northeast Tennessee, East Tennessee State University, PO Box 70577, Johnson City, TN 37614, USA.

出版信息

Neurotox Res. 1999 Sep;1(1):3-25. doi: 10.1007/BF03033336.

DOI:10.1007/BF03033336
PMID:12835111
Abstract

For centuries, starting with the advent of the microscope, cytotoxins have been known to non-selectively destroy nerves and other tissue cells. However, neurotoxins restricted in effect to one kind of neuron are an invention of the 20th century. One might reasonably trace the origins of this field to 1960 when the Nobel Laureates, R. Levi- Montalcini and S Cohen, showed that an antibody to nerve growth factor effectively prevented development of sympathetic nerves in the absence of overt changes in dorsal root ganglia and other neural and non-neural tissues. The year 1967 marks discovery of 6-hydroxydopamine, the first of dozens of chemically-selective neurotoxins. As stated by the physiologist W.B. Cannon, neural function can be deduced by denoting absence-deficits. A wealth of knowledge in neuroscience has been realized through use of neurotoxins. In the 21st century we foresee neurotoxins for virtually all neurochemically-identifiable or receptor-specific neurons, acting at/via functional proteins or characteristic DNA sites. These tools will provide us with a better means to probe the mind and thereby lead to a fuller understanding of the intricate roles of identifiable neuronal systems in integrative neuroscience.

摘要

几个世纪以来,自显微镜问世起,人们就知道细胞毒素会非选择性地破坏神经和其他组织细胞。然而,作用仅限于一种神经元的神经毒素是20世纪的发明。人们可以合理地将这个领域的起源追溯到1960年,当时诺贝尔奖获得者R. 莱维-蒙塔尔奇尼和S. 科恩表明,神经生长因子抗体在背根神经节以及其他神经和非神经组织没有明显变化的情况下,有效地阻止了交感神经的发育。1967年发现了6-羟基多巴胺,这是几十种化学选择性神经毒素中的第一种。正如生理学家W.B. 坎农所说,通过指出缺失缺陷可以推断神经功能。通过使用神经毒素,神经科学领域已经积累了丰富的知识。在21世纪,我们预见到几乎所有神经化学可识别或受体特异性神经元的神经毒素,作用于/通过功能蛋白或特征性DNA位点。这些工具将为我们提供更好的方法来探究大脑,从而更全面地理解可识别神经元系统在整合神经科学中的复杂作用。

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