Tumor necrosis factor-α increases brain-derived neurotrophic factor expression in trigeminal ganglion neurons in an activity-dependent manner.
Tumor necrosis factor-α increases brain-derived neurotrophic factor expression in trigeminal ganglion neurons in an activity-dependent manner.
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DOI：
10.1016/j.neuroscience.2011.02.028
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发表时间：
2011-04-28
期刊：
影响因子：
3.3
通讯作者：
Balkowiec, A.
中科院分区：
文献类型：
--
作者：
Balkowiec-Iskra, E.;Vermehren-Schmaedick, A.;Balkowiec, A.
许多慢性三叉神经疼痛病症，如偏头痛或颞下颌关节紊乱，与三叉神经节（TG）感觉神经元外周末梢内的炎症有关。在神经炎症机制中的关键作用归因于促炎细胞因子，例如白细胞介素-1 β和肿瘤坏死因子-α（TNFα），它们也有助于神经损伤引起的持续性神经性疼痛机制。然而，马槟榔碱介导的突触可塑性和伤害性感受器敏化的机制尚未完全了解。在本研究中，我们研究了TNFα对脑源性神经营养因子（BDNF）神经元表达的影响，BDNF在突触可塑性和伤害性通路的敏化中的作用已被充分证明。我们发现，在富含神经元的大鼠TG分离培养物中，TNFα处理4小时和24小时分别增加BDNF mRNA和蛋白。TNFα可增加环磷酸腺苷反应元件结合蛋白（CREB）的磷酸化形式，CREB是一种参与调节神经元中BDNF表达的转录因子，可激活BDNF外显子IV（前外显子III）的转录，并在较小程度上激活外显子VI（前外显子IV），但不激活外显子I。TNFα介导的BDNF表达增加伴随着降钙素基因相关肽（CGRP）的增加，这与先前发表的研究一致，并表明两种肽在TG神经元中受到炎症介质的类似调节。TNFα对BDNF表达的影响依赖于通过TTX敏感通道的钠内流和p38-丝裂原活化蛋白激酶。此外，电刺激和毛喉素，已知增加细胞内cAMP，加强TNFα介导的BDNF表达上调。本研究为促炎细胞因子对TG初级感觉神经元的直接作用提供了新的证据，并揭示了TNFα刺激这些神经元中BDNF从头合成的机制。因此，TNFα应被认为是BDNF依赖的神经元可塑性的机制。
Many chronic trigeminal pain conditions, such as migraine or temporo-mandibular disorders, are associated with inflammation within peripheral endings of trigeminal ganglion (TG) sensory neurons. A critical role in mechanisms of neuroinflammation is attributed to proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α (TNFα) that also contribute to mechanisms of persistent neuropathic pain resulting from nerve injury. However, the mechanisms of cytokine-mediated synaptic plasticity and nociceptor sensitization are not completely understood. In the present study, we examined the effects of TNFα on neuronal expression of brain-derived neurotrophic factor (BDNF), whose role in synaptic plasticity and sensitization of nociceptive pathways is well documented. We show that 4- and 24-hr treatment with TNFα increases BDNF mRNA and protein, respectively, in neuron-enriched dissociated cultures of rat TG. TNFα increases the phosphorylated form of the cyclic adenosine monophosphate-responsive element binding protein (CREB), a transcription factor involved in regulation of BDNF expression in neurons, and activates transcription of BDNF exon IV (former exon III) and, to a lesser extent, exon VI (former exon IV), but not exon I. TNFα-mediated increase in BDNF expression was accompanied by increase in calcitonin gene-related peptide (CGRP), which is consistent with previously published studies, and indicates that both peptides are similarly regulated in TG neurons by inflammatory mediators. The effect of TNFα on BDNF expression is dependent on sodium influx through TTX-sensitive channels and on p38-mitogen-activated protein kinase. Moreover, electrical stimulation and forskolin, known to increase intracellular cAMP, potentiate the TNFα-mediated upregulation of BDNF expression. This study provides new evidence for a direct action of proinflammatory cytokines on TG primary sensory neurons, and reveals a mechanism through which TNFα stimulates de novo synthesis of BDNF in these neurons. Thus, TNFα should be considered in mechanisms of BDNF-dependent neuronal plasticity.
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DOI：
10.1523/jneurosci.3295-09.2010
发表时间：
2010-01-13
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Clark AK;Staniland AA;Marchand F;Kaan TK;McMahon SB;Malcangio M
通讯作者：
Malcangio M
影响因子：
2.9
作者：
Cho, HJ;Kim, JK;Rush, RA
通讯作者：
Rush, RA
DOI：
10.1523/jneurosci.3795-08.2008
发表时间：
2008-12-24
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Binshtok AM;Wang H;Zimmermann K;Amaya F;Vardeh D;Shi L;Brenner GJ;Ji RR;Bean BP;Woolf CJ;Samad TA
通讯作者：
Samad TA
影响因子：
5.3
作者：
Guo, W;Robbins, MT;Ren, K
通讯作者：
Ren, K
影响因子：
2.9
作者：
Cho, HJ;Kim, SY;Chu, MY
通讯作者：
Chu, MY