Reciprocal changes in the expression of Bcl-2 and Bax in hypoglossal nucleus after axotomy in adult rats: possible involvement in the induction of neuronal cell death

Reciprocal changes in the expression of Bcl-2 and Bax in hypoglossal nucleus after axotomy in adult rats: possible involvement in the induction of neuronal cell death
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DOI:
10.1016/s0006-8993(99)01315-3
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发表时间:
1999-05-08
期刊:
影响因子:
2.9
通讯作者:
Mizuno, A
Mizuno, A
中科院分区:
医学3区
文献类型:
--
作者:
Baba, N;Koji, T;Mizuno, A

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哺乳动物新生儿神经元发育的大量研究表明,神经细胞死亡后,轴截本质上是凋亡。然而,在成年动物中,轴突损伤后的神经元细胞死亡可能表现出也可能不表现出细胞凋亡的特征。Bcl-2和Bax分别是细胞凋亡的抑制蛋白和启动蛋白。为了研究这些蛋白与成年动物舌下神经切断后神经元细胞死亡的关系,我们对成年雄性Wister大鼠进行了右侧舌下神经切断,并在切断后的不同时间间隔处死大鼠。我们用免疫组织化学方法分析了成年大鼠舌下核中Bcl-2和Bax的表达。我们的分析显示,在轴突切开术后3天,相对于舌下核运动神经元总数而言,bax阳性运动神经元的百分比有所增加。与此相反,在同一时间间隔内,bcl -2阳性运动神经元占运动神经元总数的比例较低。定量分析单个神经元中Bcl-2和Bax的信号强度显示,切开后7 d, Bax免疫染色显著升高,而Bcl-2阳性神经元中大部分Bcl-2免疫染色强度下降。我们的研究结果证实了成年大鼠割轴后运动神经元细胞死亡的发生,并且Bcl-2/Bax表达的互变与运动神经元的丧失存在密切的时间关系。这些结果提示Bcl-2/Bax系统可能参与了成年大鼠腋切开术后神经元细胞凋亡的诱导。(C) 1999 Elsevier Science B.V.版权所有
Numerous studies of neonatal neuronal development in mammals have revealed that neuronal cell death following axotomy is apoptotic in nature. In adult animals, however, neuronal cell death following axonal injury may or may not exhibit features of apoptosis. Bcl-2 and Bax have been identified as inhibitor and promoter proteins, respectively, of apoptosis. To investigate the relationship between these proteins and neuronal cell death following axotomy in adult animals, we performed axotomy of the right hypoglossal nerve in adult male Wister rats, and sacrificed the rats at various intervals after axotomy. We analyzed the expression of Bcl-2 and Bax immunohistochemically in the hypoglossal nuclei of the adult rats following axotomy. Our analysis showed an increase in the percentage of Bax-positive motoneurons relative to the total number of motoneurons in the hypoglossal nucleus on the axotomy side at three days after axotomy. In contrast, a low percentage of Bcl-2-positive motoneurons to the total number of motoneurons was noted at the same time interval after axotomy. Quantitative analysis of the signal intensity for Bcl-2 and Bax in individual neurons showed that Bax immunostaining significantly increased 7 days after axotomy, while the intensity of Bcl-2 immunostaining decreased in most of Bcl-2-positive neurons. Our results confirmed the occurrence of motoneuron cell death in adult rats after axotomy, and that a close temporal relationship exists between the reciprocal changes in Bcl-2/Bax expression and the loss of motoneurons. These results indicate the possible involvement of the Bcl-2/Bax system in the induction of neuronal cell apoptosis after axotomy in adult rats. (C) 1999 Elsevier Science B.V. All rights reserved.