Axotomized neonatal motoneurons overexpressing the bcl2 proto-oncogene retain functional electrophysiological properties
Axotomized neonatal motoneurons overexpressing the bcl2 proto-oncogene retain functional electrophysiological properties
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DOI：
10.1073/pnas.93.9.3978
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发表时间：
1996-04-30
影响因子：
11.1
通讯作者：
DuboisDauphin, M
中科院分区：
文献类型：
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作者：
Alberi, S;Raggenbass, M;DuboisDauphin, M
Bcl 2过表达可防止轴突切断诱导的新生面部运动神经元死亡，如形态学标准所定义的，然而，这些存活的受损转基因神经元的功能特性尚不清楚。使用过表达Bcl 2蛋白的转基因小鼠，我们研究了新生儿单侧轴突切断后7至20天转基因面运动神经元的生物电特性，使用脑干切片和全细胞膜片钳记录。野生型和转基因小鼠的Nonaxotomized面部运动神经元具有相似的特性，他们有一个输入电阻38 +/- 6 M Ω和发射后，注射正电流脉冲重复。当细胞在其静息膜电位或接近其静息膜电位时被电压阻尼时，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）、N-甲基-D-天冬氨酸（NMDA）或加压素产生持续的内向电流。在转基因轴突切断小鼠中，可以发现面部运动神经元位于病变同侧;它们的输入电阻为150 +/- 30 M Ω，表明它们体积较小，重复放电，并且对AMPA，NMDA和加压素也有反应。损伤后1周的形态学测量表明，脑源性神经营养因子的应用防止了轴突切断转基因运动神经元的大小减少。这些数据表明，Bcl 2不仅可以防止形态学的轴突切断新生转基因运动神经元的凋亡，但也允许运动神经元保存功能的电生理特性。
Bcl2 overexpression prevents axotomy-induced neuronal death of neonatal facial motoneurons, as defined by morphological criteria, However, the functional properties of these surviving lesioned transgenic neurons are unknown. Using transgenic mice overexpressing the protein Bcl2, we have investigated the bioelectrical properties of transgenic facial motoneurons from 7 to 20 days after neonatal unilateral axotomy using brain-stem slices and whole-cell patch-clamp recording. Nonaxotomized facial motoneurons from wild-type and transgenic mice had similar properties; they had an input resistance of 38 +/- 6 M Omega and fired repetitively after injection of positive current pulses. When cells were voltage-damped at or near their resting membrane potential alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartic acid (NMDA), or vasopressin generated sustained inward currents. In transgenic axotomized mice, facial motoneurons could be found located ipsilaterally to the lesion; they had an input resistance of 150 +/- 30 M Omega, indicating that they were smaller in size, fired repetitively, and were also responsive to AMPA, NMDA, and vasopressin. Morphological measurements achieved 1 week after the lesion have shown that application of brain-derived neurotrophic factor prevented the reduction in size of axotomized transgenic motoneurons. These data indicate that Bcl2 not only prevents morphological apoptotic death of axotomized neonatal transgenic motoneurons but also permits motoneurons to conserve functional electrophysiological properties.