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转化生长因子-β2调节海马神经元的突触效能和可塑性,并诱导CREB磷酸化。

Transforming growth factor-beta2 modulates synaptic efficacy and plasticity and induces phosphorylation of CREB in hippocampal neurons.

作者信息

Fukushima Teruyuki, Liu Rong-Yu, Byrne John H

机构信息

Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.

出版信息

Hippocampus. 2007;17(1):5-9. doi: 10.1002/hipo.20243.

DOI:10.1002/hipo.20243
PMID:17094084
Abstract

Transforming growth factor-betas (TGF-betas) are widely expressed and play roles as multifunctional growth factors and regulators of key events in development, disease, and repair. However, it is not known whether TGF-betas affect the plasticity of hippocampal neurons. As a first step to address this issue, we examined whether TGF-beta2 modulated the electrophysiological and biochemical properties of cultured hippocampal neurons. We found that prolonged 24 h treatment with TGF-beta2 induced facilitation of evoked postsynaptic currents (ePSCs). This facilitation was associated with a decrease in short-term synaptic depression of ePSCs and increases in both the amplitude and frequency of spontaneous miniature postsynaptic currents (mPSCs). The long-term changes of ePSCs and mPSCs may be associated with cAMP response element-binding protein (CREB), which has been previously implicated in long-term potentiation. Immunofluorescence techniques and Western blot analysis both revealed that TGF-beta2 enhanced the phosphorylation of CREB. Together, these results suggest that TGF-beta2 may play a role in the cascade of events underlying long-term synaptic facilitation in hippocampus, and that CREB may be an important mediator of these effects.

摘要

转化生长因子-β(TGF-β)广泛表达,并作为多功能生长因子以及发育、疾病和修复过程中关键事件的调节因子发挥作用。然而,尚不清楚TGF-β是否会影响海马神经元的可塑性。作为解决该问题的第一步,我们研究了TGF-β2是否调节培养的海马神经元的电生理和生化特性。我们发现,用TGF-β2进行24小时的长时间处理会诱导诱发突触后电流(ePSC)的易化。这种易化与ePSC的短期突触抑制的降低以及自发微小突触后电流(mPSC)的幅度和频率的增加有关。ePSC和mPSC的长期变化可能与cAMP反应元件结合蛋白(CREB)有关,CREB先前已被证明与长期增强有关。免疫荧光技术和蛋白质印迹分析均显示,TGF-β2增强了CREB的磷酸化。总之,这些结果表明,TGF-β2可能在海马长期突触易化的一系列事件中发挥作用,并且CREB可能是这些作用的重要介导因子。

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