Gervasi Christine, Thyagarajan Amar, Szaro Ben G
Department of Biological Sciences, State University of New York--University at Albany, Albany, New York 12222, USA.
J Comp Neurol. 2003 Jun 23;461(2):262-75. doi: 10.1002/cne.10695.
Characteristic changes in the expression of neuronal intermediate filaments (nIFs), an abundant cytoskeletal component of vertebrate axons, accompany successful axon regeneration. In mammalian regenerating PNS, expression of nIFs that are characteristic of mature neurons becomes suppressed throughout regeneration, whereas that of peripherin, which is abundant in developing axons, increases. Comparable changes are absent from mammalian injured CNS; but in goldfish and lamprey CNS, expression of several nIFs increases during axon regrowth. To obtain a broader view of the nIF response of successfully regenerating vertebrate CNS, in situ hybridization and video densitometry were used to track multiple nIF mRNAs during optic axon regeneration in Xenopus laevis. As in other successfully regenerating systems, peripherin expression increased rapidly after injury and expression of those nIFs characteristic of mature retinal ganglion cells decreased. Unlike the decrease in nIF mRNAs of regenerating PNS, that of Xenopus retinal ganglion cells was transient, with most nIF mRNAs increasing above normal during axon regrowth. At the peak of regeneration, increases in each nIF mRNA resulted in a doubling of the total amount of nIF mRNA, as well as a shift in the relative proportions contributed by each nIF. The relative proportions of peripherin and NF-M increased above normal, whereas proportions of xefiltin and NF-L decreased and that of XNIF remained the same. The increases in peripherin and NF-M mRNAs were accompanied by increases in protein. These results are consistent with the hypothesis that successful axon regeneration involves changes in nIF subunit composition conducive to growth and argue that a successful injury response differs between CNS and PNS.
神经元中间丝（nIFs）是脊椎动物轴突中丰富的细胞骨架成分，其表达的特征性变化伴随着轴突的成功再生。在哺乳动物再生的周围神经系统（PNS）中，成熟神经元特有的nIFs表达在整个再生过程中受到抑制，而在发育中的轴突中丰富的外周蛋白表达增加。哺乳动物受损的中枢神经系统（CNS）中没有类似的变化；但在金鱼和七鳃鳗的中枢神经系统中，几种nIFs的表达在轴突再生过程中增加。为了更全面地了解成功再生的脊椎动物中枢神经系统的nIF反应，利用原位杂交和视频密度测定法追踪非洲爪蟾视轴突再生过程中的多种nIF mRNA。与其他成功再生的系统一样，损伤后外周蛋白表达迅速增加，成熟视网膜神经节细胞特有的nIFs表达下降。与再生的周围神经系统中nIF mRNA的减少不同，非洲爪蟾视网膜神经节细胞的nIF mRNA减少是短暂的，大多数nIF mRNA在轴突再生过程中增加到正常水平以上。在再生高峰期，每种nIF mRNA的增加导致nIF mRNA总量增加一倍，同时每种nIF所贡献的相对比例也发生了变化。外周蛋白和神经丝蛋白M（NF-M）的相对比例增加到正常水平以上，而xefiltin和神经丝蛋白L（NF-L）的比例下降，XNIF的比例保持不变。外周蛋白和NF-M mRNA的增加伴随着蛋白质的增加。这些结果与以下假设一致，即成功的轴突再生涉及有利于生长的nIF亚基组成的变化，并表明中枢神经系统和周围神经系统的成功损伤反应有所不同。
