Expression of DNA methyltransferases in adult dorsal root ganglia is cell-type specific and up regulated in a rodent model of neuropathic pain.
Expression of DNA methyltransferases in adult dorsal root ganglia is cell-type specific and up regulated in a rodent model of neuropathic pain.
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DOI：
10.3389/fncel.2014.00217
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发表时间：
2014
影响因子：
5.3
通讯作者：
Martina M
中科院分区：
文献类型：
--
作者：
Pollema-Mays SL;Centeno MV;Apkarian AV;Martina M
神经性疼痛与背根神经节（DRG）神经元的高兴奋性和内在放电有关。这些表型变化可能是持久的，可能跨越动物模型的整个生命周期，并依赖于许多蛋白质表达的改变，包括许多离子通道。然而，DRGs如何维持神经病变条件下蛋白表达的长期变化仍不清楚。DNA甲基化是一种众所周知的基因表达的表观遗传控制机制，它是通过三种酶的作用来实现的：DNA甲基转移酶（DNMT） 1、3a和3b，这些酶主要在发育过程中被研究。我们首先通过免疫组织化学分析来评估这些酶是否在成年大鼠DRGs （L4-5）中表达，发现DNMT1在胶质细胞和神经元中均有表达，DNMT3a优先在胶质细胞中表达，DNMT3b优先在神经元中表达。然后使用神经性疼痛大鼠模型来确定神经损伤是否会在疼痛发作后多个时间点诱导DRGs的表观遗传变化。实时RT - PCR分析显示，同侧神经损伤（SNI）的同侧DRGs中DNMT转录物表达有明显的时间依赖性变化，而假手术大鼠则没有。有趣的是，DNMT3b转录显示出强劲的上调，在手术后1周就出现了，并持续到4周（我们的终点）；相比之下，DNMT1和DNMT3a转录本仅显示短暂的中度上调，直到第二周才出现。我们认为，DNMT在成人DRGs中的调节可能是疼痛表型的一个因素，值得进一步研究。
Neuropathic pain is associated with hyperexcitability and intrinsic firing of dorsal root ganglia (DRG) neurons. These phenotypical changes can be long lasting, potentially spanning the entire life of animal models, and depend on altered expression of numerous proteins, including many ion channels. Yet, how DRGs maintain long-term changes in protein expression in neuropathic conditions remains unclear. DNA methylation is a well-known mechanism of epigenetic control of gene expression and is achieved by the action of three enzymes: DNA methyltransferase (DNMT) 1, 3a, and 3b, which have been studied primarily during development. We first performed immunohistochemical analysis to assess whether these enzymes are expressed in adult rat DRGs (L4–5) and found that DNMT1 is expressed in both glia and neurons, DNMT3a is preferentially expressed in glia and DNMT3b is preferentially expressed in neurons. A rat model of neuropathic pain was then used to determine whether nerve injury may induce epigenetic changes in DRGs at multiple time points after pain onset. Real-time RT PCR analysis revealed robust and time-dependent changes in DNMT transcript expression in ipsilateral DRGs from spared nerve injury (SNI) but not sham rats. Interestingly, DNMT3b transcript showed a robust upregulation that appeared already 1 week after surgery and persisted at 4 weeks (our endpoint); in contrast, DNMT1 and DNMT3a transcripts showed only moderate upregulation that was transient and did not appear until the second week. We suggest that DNMT regulation in adult DRGs may be a contributor to the pain phenotype and merits further study.
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影响因子：
16.2
作者：
Baliki, Marwan N.;Geha, Paul Y.;Fields, Howard L.;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania
影响因子：
7.5
作者：
Dupont, Catherine;Gribnau, Joost
通讯作者：
Gribnau, Joost
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping
影响因子：
4.8
作者：
Bachman, KE;Rountree, MR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
5.6
作者：
BESTOR, T;LAUDANO, A;INGRAM, V
通讯作者：
INGRAM, V