Cell death and axon regeneration of Purkinje cells after axotomy: Challenges of classical hypotheses of axon regeneration
Cell death and axon regeneration of Purkinje cells after axotomy: Challenges of classical hypotheses of axon regeneration
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DOI：
10.1016/j.brainresrev.2004.11.007
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发表时间：
2005-09-01
影响因子：
--
通讯作者：
Sotelo, C
中科院分区：
文献类型：
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作者：
Dusart, I;Ghoumari, A;Sotelo, C
尽管在一定条件下，成年哺乳动物神经元能够在周围神经系统中再生轴突，但在中枢神经系统中却不能。被切断的轴突周围的环境似乎是轴突再生的关键因素。许多旨在促进成年哺乳动物中枢神经系统轴突再生的研究已经成功地通过添加生长许可分子和/或中和生长抑制分子来操纵这种环境。在这两种情况下，能够再生的轴突数量都很低，不同的神经元群体在再生反应中也不相等，这表明对环境的操纵并不总是足够的。这在小脑系统中得到了很好的说明，在小脑系统中，当面对一个允许的环境时，axoized的下橄榄神经元会再生，而成熟的浦肯野细胞则不会。神经元再生其轴突的内在能力通常与其对轴突切开术的反应强度（分子表达，死亡概率）相关。此外，GAP-43（生长相关分子）和c-Jun等分子参与轴突再生和细胞死亡，这表明这两个过程是相关的。令人惊讶的是，浦肯野细胞在发育过程中失去了轴突再生的能力（即使在没有髓磷脂的情况下），然后才失去了对轴突切除的反应能力。这些结果强调了不同神经元类型对轴突切除的不同反应，并强调在浦肯野细胞中，两种细胞决定（轴突再生和细胞死亡）受到不同的调节，因此不是同一信号通路的一部分。(c) 2004 Elsevier B.V.版权所有
Although adult mammalian neurons are able to regenerate their axons in the peripheral nervous system under certain conditions, they are not able to do it in the central nervous system. The environment surrounding the severed axons appears to be a key factor for axon regeneration. Many studies aiming to enhance axon regeneration in the CNS of adult mammals have successfully manipulated this environment by adding growth permissive molecules and/or neutralizing growth inhibitory molecules. In both cases, the number of axons able to regenerate was low and the different neuronal populations were not equal in their regenerative response, suggesting that manipulation of the environment is not always sufficient. This is particularly well illustrated in the cerebellar system, in which axotomized inferior olivary neurons regenerate when confronted with a permissive environment, whereas mature Purkinje cells do not. The intrinsic ability of a neuron to regenerate its axon is generally correlated with the intensity of its reaction to axotomy (expression of molecules, probability to die). Furthermore, molecules such as GAP-43 (growth-associated molecule) and c-Jun are involved in both axon regeneration and cell death suggesting that these two processes are linked. Surprisingly, Purkinje cells lose their capacity to regenerate their axon (even in the absence of myelin) during development before losing their capacity to react to an axotomy by cell death. These results emphasize the different reactions to axotomy between neuron types and underline that in Purkinje cells, the two cell decisions (axon regeneration and cell death) are differently regulated and therefore not part of the same signaling pathway. (c) 2004 Elsevier B.V. All rights reserved.