Continuous infusion of neurotrophin-3 triggers sprouting, decreases the levels of TrkA and TrkC and inhibits epileptogenesis and activity-dependent axonal growth in adult rats
Continuous infusion of neurotrophin-3 triggers sprouting, decreases the levels of TrkA and TrkC and inhibits epileptogenesis and activity-dependent axonal growth in adult rats
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DOI：
10.1016/s0306-4522(02)00384-6
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发表时间：
2002-01-01
期刊：
影响因子：
3.3
通讯作者：
Fahnestock, M
中科院分区：
文献类型：
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作者：
Xu, B;Michalski, B;Fahnestock, M
神经营养因子-3（NT-3）是神经营养因子家族的成员，对细胞存活、轴突生长和神经元可塑性具有重要作用。癫痫样激活可以调节神经营养因子的表达，神经营养因子的增加或减少可以影响癫痫发生和癫痫相关的轴突生长。有趣的是，神经生长因子和脑源性神经营养因子的表达在癫痫发作后迅速上调，而NT-3 mRNA保持不变或经历延迟的下调，这表明NT-3可能在癫痫发生中具有不同的功能。在本研究中，我们表明，连续脑室内灌注NT-3在点燃的情况下触发苔藓纤维发芽的内部分子层的齿状回和层的CA 3区域的oriens。此外，尽管这种NT-3相关的发芽效应，连续输注NT-3延缓行为性癫痫发作的发展，并抑制点燃诱导的苔藓纤维发芽的内部分子层的齿状回。我们还表明，长期输注NT-3导致减少点燃诱导的Trk磷酸化和下调的高亲和力的Trk受体，TrkA和TrkC，这表明参与胆碱能神经生长因子受体和海马NT-3受体在这些影响。我们的研究结果表明NT-3在癫痫发作发展和癫痫相关的突触重组中具有重要的抑制作用，（C）2002 IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
Neurotrophin-3 (NT-3), a member of the neurotrophin family of neurotrophic factors, is important for cell survival, axonal growth and neuronal plasticity. Epileptiform activation can regulate the expression of neurotrophins, and increases or decreases in neurotrophins can affect both epileptogenesis and seizure-related axonal growth. Interestingly, the expression of nerve growth factor and brain-derived neurotrophic factor is rapidly up-regulated following seizures, while NT-3 mRNA remains unchanged or undergoes a delayed down-regulation, suggesting that NT-3 might have a different function in epileptogenesis. In the present study, we demonstrate that continuous intraventricular infusion of NT-3 in the absence of kindling triggers mossy fiber sprouting in the inner molecular layer of the dentate gyrus and the stratum oriens of the CA3 region. Furthermore, despite this NT-3-related sprouting effect, continuous infusion of NT-3 retards the development of behavioral seizures and inhibits kindling-induced mossy fiber sprouting in the inner molecular layer of the dentate gyrus. We also show that prolonged infusion of NT-3 leads to a decrease in kindling-induced Trk phosphorylation and a down-regulation of the high-affinity Trk receptors, TrkA and TrkC, suggesting an involvement of both cholinergic nerve growth factor receptors and hippocampal NT-3 receptors in these effects. Our results demonstrate an important inhibitory role for NT-3 in seizure development and seizure-related synaptic reorganization, (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.