Howe Charles L
Department of Neurology, Mayo Medical and Graduate Schools, Guggenheim 442C, 200 First Street SW, Rochester, MN 55905, USA.
Neurosci Lett. 2003 Nov 6;351(1):41-5. doi: 10.1016/s0304-3940(03)00915-7.
Synaptic plasticity is clearly controlled by synaptic activity and by neurotrophin-dependent signaling. We have previously hypothesized that synaptic activity modulates concomitant neurotrophin receptor signaling, thereby integrating the activity state of a synapse with the state of neurotrophic support available at the synapse. Herein we present evidence in support of this hypothesis. Using PC12 cells as a model of the presynaptic element, we show that depolarization increases TrkA tyrosine phosphorylation in response to nerve growth factor (NGF). Moreover, we show that depolarization alone is sufficient to induce the tyrosine phosphorylation of TrkA. These findings are functionally relevant, as evidenced by our observation that depolarization alone induces neurite outgrowth, and that depolarization dramatically enhances neurite outgrowth in response to NGF, especially in primed PC12 cells. We conclude that normal synaptic function may depend upon the integration of synaptic activity and activity-dependent neurotrophin release and signaling, and that these findings have potential relevance to neural repair.
突触可塑性显然受突触活动以及神经营养因子依赖性信号传导的控制。我们之前曾假设，突触活动会调节伴随的神经营养因子受体信号传导，从而将突触的活动状态与突触处可用的神经营养支持状态整合起来。在此，我们提供证据支持这一假设。以PC12细胞作为突触前元件的模型，我们发现去极化会增加神经生长因子（NGF）刺激下TrkA的酪氨酸磷酸化。此外，我们还表明单独的去极化就足以诱导TrkA的酪氨酸磷酸化。这些发现具有功能相关性，我们观察到单独的去极化会诱导神经突生长，并且去极化会显著增强对NGF的神经突生长反应，尤其是在预处理的PC12细胞中，这证明了这一点。我们得出结论，正常的突触功能可能依赖于突触活动与活动依赖性神经营养因子释放及信号传导的整合，并且这些发现与神经修复可能相关。
