NEUROFILAMENT GENE-EXPRESSION - A MAJOR DETERMINANT OF AXONAL CALIBER
NEUROFILAMENT GENE-EXPRESSION - A MAJOR DETERMINANT OF AXONAL CALIBER
复制标题
DOI：
10.1073/pnas.84.10.3472
复制
发表时间：
1987-05-01
影响因子：
11.1
通讯作者：
PRICE, DL
中科院分区：
文献类型：
--
作者：
HOFFMAN, PN;CLEVELAND, DW;PRICE, DL
在哺乳动物神经纤维中出现的广泛的轴突直径范围内，每类神经元的轴突直径范围相对有限。管径的控制具有功能意义，管径是有髓神经纤维传导速度的主要决定因素。以往的观察结果支持神经细丝是大型有髓神经纤维轴突口径的主要内在决定因素的假说。在通过挤压或切断周围神经切断轴突(轴突切断)之后，从细胞体延伸到轴突切断部位的近端轴突残端的口径变小。(与细胞体断开的远端轴突残端退化，代之以近端残端长出的再生轴突。)近端残端轴突口径的减少与这些轴突中经历缓慢轴突运输的核因子蛋白的选择性减少、轴突核因子含量的减少以及传导速度的减慢有关。本报告证明轴突切断后轴突口径的改变与NF基因表达的选择性改变有关。用特异的cDNA杂交技术检测大鼠坐骨神经损伤后不同时间腰感觉神经元中68 kDa神经细丝蛋白(NF68)、β-微管蛋白和肌动蛋白的表达水平。神经切断后4~42d，NF68基因表达水平下降2~3倍。与此同时，微管蛋白和肌动蛋白的mRNAs水平增加了几倍。这些发现支持这样一种假设，即一组神经元特异性基因(编码核因子)的表达直接决定了轴突口径，轴突口径是神经元形态的一个特征，对生理和行为具有重要影响。
Within the wide spectrum of axonal diameters occurring in mammalian nerve fibers, each class of neurons has a relatively restricted range of axonal calibers. The control of caliber has functional significance between diameter is the principal determinant of conduction velocity in myelinated nerve fibers. Previous observations support the hypothesis that neurofilaments (NF) are major intrinsic determinants of axonal caliber in large myelinated nerve fibers. Following interruption of axons (axotomy) by crushing or cutting a peripheral nerve, caliber is reduced in the proximal axonal stumps, which extend from the cell bodies to the site of axotomy. (The distal axonal stumps, which are disconnected from the cell bodies, degenerate and are replaced by the outgrowth of regenerating axonal sprouts arising from the proximal stumps.) This reduction in axonal caliber in the proximal stumps is associated with a selective diminution in the amount of NF protein undergoing slow axonal transport in these axons, with a decrease in axonal NF content, and with reduced conduction velocity. The present report demonstrates that changes in axonal caliber after axotomy correlate with a selective alteration in NF gene expression. Hybridization with specific cDNAs was used to measure levels of mRNA encoding the 68-kDa neurofilament protein (NF68), .beta.-tubulin, and actin in lumbar sensory neurons of rat at various times after crushing the sciatic nerve. Between 4 and 42 days after axotomy by nerve crush, the levels of NF68 mRNA were reduced 2- to 3-fold. At the same times, the levels of tubulin and actin mRNAs were increased several-fold. These findings support the hypothesis that the expression of a single set of neuron-specific genes (encoding NF) directly determines axonal caliber, a feature of neuronal morphology with important consequences for physiology and behavior.