Extrinsic regulation of injury/growth-related gene expression in the inferior olive of the adult rat
Extrinsic regulation of injury/growth-related gene expression in the inferior olive of the adult rat
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DOI：
10.1046/j.1460-9568.2003.02940.x
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发表时间：
2003-10-01
影响因子：
3.4
通讯作者：
Strata, P
中科院分区：
文献类型：
--
作者：
Buffo, A;Carulli, D;Strata, P
成功的轴突再生依赖于受损神经元上调一组特定的损伤/生长相关基因的能力。在成人中枢神经系统中，细胞体反应的强度通常与损伤部位与核周体的距离有关，近端损伤更强。然而，下橄榄（IO）细胞的反应损伤和再生的轴突，即使在远端横断。为了研究调节IO生长特性的机制，我们研究了在沿沿着橄榄小脑通路的不同位点进行靶向缺失或轴突切断后损伤/生长标志物（一氧化氮合酶、生长相关蛋白43和c-Jun）的表达。轴突损伤和靶点丢失都揭示了精确亚核内分布的IO神经元的两个子集：一个子集在所有条件下上调所有标记物，而另一个子集显示出轻度的c-Jun表达，但即使在非常近端的轴突切断术后仍然没有反应。这些观察结果表明，不同的IO细胞亚群响应不同的监管策略。无反应神经元对环境的积极或消极线索不敏感，这表明它们本质上无法对损伤建立细胞反应。相反，反应性神经元中的细胞体变化是在去除逆向运输的靶源性抑制信号后引起的。目标损失也诱导IO细胞的退化，其存活在成年期仍然部分依赖于浦肯野靶点。因此，功能同质群体的内在再生潜力受到多种机制的调控，这些机制对不同的神经元亚群具有特异性。
Successful axon regeneration relies on the capability of the lesioned neurons to up-regulate a specific set of injury/growth-associated genes. In the adult central nervous system, the strength of the cell body response is generally related to the distance of the injury site from the perikaryon, being stronger for proximal lesions. Nevertheless, inferior olive (IO) cells react to injury and regenerate their axons even after distal transections. To investigate the mechanisms that regulate the IO growth properties, we examined the expression of injury/growth markers (nitric oxide synthase, growth-associated protein 43 and c-Jun) after target deletion or axotomy performed at different sites along the olivocerebellar pathway. Both axon injury and target loss disclose two subsets of IO neurons distributed within precise subnuclei: one subset up-regulates all markers in all conditions, whereas the other shows a mild c-Jun expression but remains unresponsive even after a very proximal axotomy. These observations indicate that distinct subpopulations of IO cells respond to different regulatory strategies. Unresponsive neurons appear insensitive to environmental positive or negative cues, suggesting that they are intrinsically unable to set up a cellular reaction to injury. In contrast, cell body changes in reactive neurons are elicited after the removal of retrogradely transported target-derived inhibitory signals. Target loss also induces degeneration of IO cells, whose survival remains partially dependent on Purkinje targets in adulthood. Thus, the intrinsic regenerative potential of a functionally homogeneous population is regulated by multiple mechanisms, specific for distinct neuronal subsets.