Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex.
Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex.
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DOI：
10.1186/1744-8069-9-21
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发表时间：
2013-04-18
期刊：
影响因子：
3.3
通讯作者：
Szyf M
中科院分区：
文献类型：
--
作者：
Alvarado S;Tajerian M;Millecamps M;Suderman M;Stone LS;Szyf M
周围神经损伤可具有长期后果，包括疼痛相关的表现，例如对皮肤刺激的超敏反应，以及情感和认知障碍，表明脊髓上机制的参与。据报道，与许多慢性疼痛状况相关的脑结构和皮质功能的变化发生在前额叶皮质（PFC）。前额叶皮层与疼痛相关的并发症有关，如抑郁、焦虑和情感决策能力受损。我们最近报道，该区域在周围神经损伤后发生了显着的表观遗传重编程，PFC中疼痛相关的结构，功能和表观遗传异常的正常化都与有效的疼痛减轻有关。在这项研究中，我们使用的坐骨神经损伤（SNI）模型的神经性疼痛，以测试的假设，周围神经损伤触发持续的持久变化的基因表达的PFC，改变功能基因网络，从而提供了一个可能的解释慢性疼痛相关的行为。SNI或假手术在三个月大的雄性CD 1小鼠中进行。损伤后6个月，我们进行了全转录组测序（RNAseq），结果显示神经损伤小鼠与对照小鼠PFC中有1147个差异调节的转录本。基因表达的变化发生在许多编码主要生物过程的功能基因簇中，如通过不相容性途径分析所揭示的。显著改变的生物过程包括神经系统疾病、骨骼肌疾病、行为和心理障碍。通过RT-QPCR验证了RNAseq检测到的几种变化，包括在慢性疼痛和/或神经元可塑性中具有已知作用的转录物，包括NMDA受体（谷氨酸受体，离子型，NMDA; grin 1），神经突生长（环岛3;机器人3）、神经胶质增生（胶质纤维酸性蛋白; GFAP），囊泡释放（synaptotagmin 2; syt 2）和神经元兴奋性（电压门控钠通道，I型; scn 1a）。这项研究使用了一种无偏见的方法来记录周围神经损伤后大脑中基因表达的长期变化。我们认为，这些变化是作为一种记忆的侮辱，是时间和空间上远离最初的伤害。
Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction. In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors. SNI or sham surgery where performed in male CD1 mice at three months of age. Six months after injury, we performed transcriptome-wide sequencing (RNAseq), which revealed 1147 differentially regulated transcripts in the PFC in nerve-injured vs. control mice. Changes in gene expression occurred across a number of functional gene clusters encoding cardinal biological processes as revealed by Ingenuity Pathway Analysis. Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders. Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein; gfap), vesicular release (synaptotagmin 2; syt2), and neuronal excitability (voltage-gated sodium channel, type I; scn1a). This study used an unbiased approach to document long-term alterations in gene expression in the brain following peripheral nerve injury. We propose that these changes are maintained as a memory of an insult that is temporally and spatially distant from the initial injury.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
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影响因子：
4.6
作者：
Couch, JA;Chen, J;Condron, BG
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Condron, BG
影响因子：
5.7
作者：
Choi, Jong Moon;Padmala, Srikanth;Pessoa, Luiz
通讯作者：
Pessoa, Luiz
影响因子：
2
作者：
Chen, Philip E.;Errington, Michael L.;Schoepfer, Ralf
通讯作者：
Schoepfer, Ralf
影响因子：
7.4
作者：
Bourquin, Anne-Frederique;Sueveges, Maria;Decosterd, Isabelle
通讯作者：
Decosterd, Isabelle