Coulpier M, Junier M P, Peschanski M, Dreyfus P A
Institut National de la Santé et de la Recherche Médicale U421, Créteil, France.
J Neurosci. 1996 Oct 1;16(19):5897-904. doi: 10.1523/JNEUROSCI.16-19-05897.1996.
The molecular events leading to motoneuronal death are still poorly understood. In mammals, the bcl-2 proto-oncogene, which encodes a membrane-associated protein, has been shown to suppress both developmental motoneuronal death and experimental axotomy-induced motoneuronal death. We assessed a potential protective effect of Bcl-2 on pathological motoneuronal death processes in adult rodents. We took advantage of the murine mutant wobbler, which undergoes progressive degeneration of the spinal and brainstem motoneurons. A hybrid carrying both the wobbler mutation and the human bcl-2 transgene under the control of the neuron-specific enolase promoter was produced. Although Bcl-2 protected spinal and brainstem motoneurons from developmental death and the postnatal motoneurons of the facial nucleus from axotomy-induced death, the pathological motoneuronal death was not altered in the adult hybrid. These results demonstrate that Bcl-2 sensitivity distinguishes at least two different motoneuronal death pathways in the wobbler mutant. They support the hypothesis that experimental and pathological motoneuronal death are dependent on different cellular mechanisms.
导致运动神经元死亡的分子事件仍未得到充分了解。在哺乳动物中，编码膜相关蛋白的bcl-2原癌基因已被证明可抑制发育性运动神经元死亡和实验性轴突切断诱导的运动神经元死亡。我们评估了Bcl-2对成年啮齿动物病理性运动神经元死亡过程的潜在保护作用。我们利用了小鼠突变体摇摆症，该突变体的脊髓和脑干运动神经元会进行性退化。构建了一个在神经元特异性烯醇化酶启动子控制下同时携带摇摆症突变和人类bcl-2转基因的杂种。尽管Bcl-2保护脊髓和脑干运动神经元免于发育性死亡，并保护面神经核的产后运动神经元免于轴突切断诱导的死亡，但成年杂种中的病理性运动神经元死亡并未改变。这些结果表明，Bcl-2敏感性区分了摇摆症突变体中至少两种不同的运动神经元死亡途径。它们支持这样的假设，即实验性和病理性运动神经元死亡依赖于不同的细胞机制。
