Co-induction of nitric oxide synthase, bcl-2 and growth-associated protein-43 in spinal motoneurons during axon regeneration in the lizard tail

被引:24
作者
Cristino, L
Pica, A
Della Corte, F
Bentivoglio, M
机构
[1] Univ Verona, Fac Med, Sect Anat & Histol, Dept Morphol & Biomed Sci, I-37134 Verona, Italy
[2] Univ Naples Federico II, Dept Evolutionary & Comparat Biol, Naples, Italy
关键词
axotomy; free radicals; neuroplasticity; neurotoxicity; gecko;
D O I
10.1016/S0306-4522(00)00393-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In lizards, tail loss transects spinal nerves and the cut axons elongate in the regrowing tail, providing a natural paradigm of robust regenerative response of injured spinal motoneurons. We previously ascertained that these events involve nitric oxide synthase induction in the axotomized motoneurons, suggesting a correlation of this enzyme with regeneration-associated gene expression. Here we investigated, in lizards, whether the cell death repressor Bcl-2 protein and growth-associated protein-43 (GAP-43) were also induced in motoneurons that innervate the regenerated tail in the first month post-caudotomy. Single and multiple immunocytochemical techniques, and quantitative image analysis, were performed. Nitric oxide synthase, GAP-43 or Bcl-2 immunoreactivity was very low or absent in spinal motoneurons of control lizards with intact tail. Nitric oxide synthase and GAP-43 were induced during the first month post-caudotomy in more than 75% of motoneurons which innnervate the regenerate. Bcl-2 was induced in approximately 95% of these motoneurons at five and 15 days, and in about 35% at one month. The intensity of Bcl-2 and GAP-43 immunostaining peaked at five days, and nitric oxide synthase at 15 days; immunoreactivity to these proteins was still significantly high at one month. Immunofluorescence revealed co-localization of nitric oxide synthase, GAP-43 and Bcl-2 in the vast majority of motoneurons at five and 15 days post-caudotomy. These findings demonstrate that co-induction of nitric oxide synthase, Bcl-2 and GAP-43 may be part of the molecular repertoire of injured motoneurons committed to survival and axon regeneration, and strongly favor a role of nitric oxide synthase in motoneuron plasticity. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:451 / 458
页数:8
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