Aberrant plasticity of peripheral sensory axons in a painful neuropathy.
Aberrant plasticity of peripheral sensory axons in a painful neuropathy.
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DOI：
10.1038/s41598-017-03390-9
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发表时间：
2017-06-13
影响因子：
4.6
通讯作者：
Nishimura I
中科院分区：
文献类型：
--
作者：
Hirai T;Mulpuri Y;Cheng Y;Xia Z;Li W;Ruangsri S;Spigelman I;Nishimura I
神经元细胞表达相当大的可塑性响应环境的线索，部分，通过亚细胞mRNA的调节。本文报道了大鼠单侧坐骨神经卡压（SNE）损伤后，外周感觉神经元胞体和轴突的mRNA分布以及3′非翻译区（3′UTR）的广泛变化。从SNE损伤和对侧L4和L5背根神经节中分离的神经元细胞在区室化系统中培养。轴突和细胞体RNA样品分别进行高通量RNA测序（RNA-Seq）。损伤的轴突表现出与蛋白质合成和神经再生相关的mRNA的富集。3′ UTR的延长在损伤的轴突中更为普遍，包括新发现的交替切割和NaV1.8 mRNA的多聚腺苷酸化。选择性多聚腺苷酸化在很大程度上独立于轴突mRNA的相对丰度，但它们在受损轴突中与RNA颗粒形成相关的功能途径中高度聚集。这些RNA-Seq数据分析表明，周围神经损伤可能导致受影响轴突中高度选择性的mRNA富集，3′UTR改变可能有助于神经病理性疼痛的机制。
Neuronal cells express considerable plasticity responding to environmental cues, in part, through subcellular mRNA regulation. Here we report on the extensive changes in distribution of mRNAs in the cell body and axon compartments of peripheral sensory neurons and the 3′ untranslated region (3′UTR) landscapes after unilateral sciatic nerve entrapment (SNE) injury in rats. Neuronal cells dissociated from SNE-injured and contralateral L4 and L5 dorsal root ganglia were cultured in a compartmentalized system. Axonal and cell body RNA samples were separately subjected to high throughput RNA sequencing (RNA-Seq). The injured axons exhibited enrichment of mRNAs related to protein synthesis and nerve regeneration. Lengthening of 3′UTRs was more prevalent in the injured axons, including the newly discovered alternative cleavage and polyadenylation of NaV1.8 mRNA. Alternative polyadenylation was largely independent from the relative abundance of axonal mRNAs; but they were highly clustered in functional pathways related to RNA granule formation in the injured axons. These RNA-Seq data analyses indicate that peripheral nerve injury may result in highly selective mRNA enrichment in the affected axons with 3′UTR alterations potentially contributing to the mechanism of neuropathic pain.