Chin Jeannie, Liu Rong-Yu, Cleary Leonard J, Eskin Arnold, Byrne John H
Department of Neurobiology and Anatomy, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
J Neurophysiol. 2006 May;95(5):3286-90. doi: 10.1152/jn.00770.2005.
Transforming growth factor beta-1 (TGF-beta1) plays important roles in the early development of the nervous system and has been implicated in neuronal plasticity in adult organisms. It induces long-term increases in sensory neuron excitability in Aplysia as well as a long-term enhancement of synaptic efficacy at sensorimotor synapses. In addition, TGF-beta1 acutely regulates synapsin phosphorylation and reduces synaptic depression induced by low-frequency stimuli. Because of the critical role of MAPK in other forms of long-term plasticity in Aplysia, we examined the role of MAPK in TGF-beta1-induced long-term changes in neuronal excitability. Prolonged (6 h) exposure to TGF-beta1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF-beta1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF-beta1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein (CREB)1, a homologue to vertebrate CREB. Both the TGF-beta1-induced long-term changes in neuronal excitability and the phosphorylation of CREB1 were blocked in the presence of an inhibitor of the MAPK cascade, confirming a role for MAPK in long-term modulation of sensory neuron function.
转化生长因子β-1（TGF-β1）在神经系统的早期发育中发挥着重要作用，并且与成年生物体中的神经元可塑性有关。它能诱导海兔感觉神经元兴奋性的长期增加，以及感觉运动突触处突触效能的长期增强。此外，TGF-β1能急性调节突触素的磷酸化，并减少低频刺激诱导的突触抑制。由于丝裂原活化蛋白激酶（MAPK）在海兔其他形式的长期可塑性中起关键作用，我们研究了MAPK在TGF-β1诱导的神经元兴奋性长期变化中的作用。长时间（6小时）暴露于TGF-β1会诱导兴奋性的长期增加。我们证实了这一发现，现在报告暴露于TGF-β1足以激活MAPK并增加活性MAPK的核水平。此外，TGF-β1增强了海兔转录激活因子环磷酸腺苷反应元件结合蛋白（CREB）1的磷酸化，CREB1是脊椎动物CREB的同源物。在存在MAPK级联抑制剂的情况下，TGF-β1诱导的神经元兴奋性长期变化和CREB1的磷酸化均被阻断，证实了MAPK在感觉神经元功能长期调节中的作用。
