REGULATION OF GENE TRANSCRIPTION AND NEURITE OUTGROWTH BY NEURAL IMPULSE

神经冲动对基因转录和神经突生长的调节

• 批准号: 5203324
• 负责人: RICHARD DOUGLAS FIELDS
• 金额: --
• 依托单位: EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203324
• 关键词: Schwann cells; action potentials; axon; biological signal transduction; calcium channel; calcium flux; cell adhesion; cell cell interaction; dendrites; genetic regulation; genetic transcription; growth cones; messenger RNA; neural cell adhesion molecules; neural transmission; neuroblastoma; oncogenes; phosphorylation; protooncogene; second messengers; transcription factor

Our studies show that expression of the neural cell adhesion molecule L1 can be regulated by action potential stimulation, by controlling levels of L1 mRNA. Regulation is selective for specific frequencies of stimulation, and for specific types of neural cell adhesion molecules (NCAM is not affected). Adhesion of neuroblastoma cells to DRG axons is reduced after 5 days electrical stimulation at the frequency that is effective in lowering L1 expression, but no changes in cell-cell adhesion are produced by stimulus patterns that do not alter L1 levels. Association of Schwann cells with axons is reduced for up to 4 days after stimulation at 0.1 Hz, but not after 1 Hz stimulation. Fasciculation of neurites can be regulated by impulse activity at an appropriate frequency. Intracellular signaling from neural impulses can be sensitive to temporal features of action potential stimulation, rather than to the concentration of second messengers or products in signaling reactions activated by the stimulus. Transcription of the c-fos gene can be more strongly activated by action potential stimuli producing low amplitude intracellular calcium transients repeated at short intervals, compared to action potential bursts that produce much larger intracellular calcium transients, repeated at less frequent intervals. Phosphorylation of the transcription factor CREB at Ser 133, does not correlate with c-fos transcription for some patterns of stimulation, particularly those consisting of intense bursts repeated at longer intervals. Accommodation of growth cones to electrically-induced collapse is associated with a decrease in trans-membrane calcium currents, which results from removal of calcium channels from the cell membrane after 24 hours of action potential stimulation at appropriate frequencies. Growth cone responses to action potentials involve different intracellular calcium signaling pathways than those activated by the receptor-mediated growth cone collapsing factor NI-35.

我们的研究表明神经细胞粘附分子 L1 的表达 可以通过动作电位刺激、控制水平来调节 L1 mRNA。 监管是针对特定频率进行选择性的 刺激，以及特定类型的神经细胞粘附分子 （NCAM 不受影响）。 神经母细胞瘤细胞与 DRG 轴突的粘附是 电刺激 5 天后减少，频率为 有效降低 L1 表达，但不改变细胞间粘附 由不改变 L1 水平的刺激模式产生。 雪旺细胞与轴突的关联在 4 天内减少 0.1 Hz 刺激，但 1 Hz 刺激后不刺激。 肌束颤动 神经突可以通过适当的脉冲活动来调节 频率。 来自神经冲动的细胞内信号传导可能对时间敏感 动作电位刺激的特征，而不是 信号反应中第二信使或产物的浓度 被刺激激活。 c-fos基因的转录可以更多 被动作电位刺激强烈激活，产生低振幅 细胞内钙瞬变以短间隔重复，比较 动作电位爆发产生更大的细胞内钙 瞬变，以较低频率的间隔重复。 磷酸化 Ser 133 处的转录因子 CREB，与 c-fos 不相关 某些刺激模式的转录，特别是那些 由以较长间隔重复的强烈爆发组成。 生长锥对电致塌陷的调节是 与跨膜钙电流的减少有关， 24 小时后从细胞膜上去除钙通道的结果 以适当的频率进行数小时的动作电位刺激。 生长 视锥细胞对动作电位的反应涉及不同的细胞内 钙信号通路比受体介导的信号通路激活 生长锥塌陷因子NI-35。