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PO2-2-14

Involvement of the long non-coding RNA Neat1 in the neuropathic pain and neurite outgrowth following nerve injury

[Speaker] Motoyo Maruyama:1,2
[Co-author] Atsushi Sakai:1, Takashi Okada:3, Hidenori Suzuki:1
1:Department of Pharmacology, Nippon Medical School, Japan, 2:Division of Laboratory Animal Science, Nippon Medical School, Japan, 3:Department of Biochemistry and Molecular Biology, Nippon Medical School, Japan

Damage to the somatosensory system such as traumatic nerve injury causes intractable neuropathic pain and/or axonal regeneration. Long non-coding RNA (lncRNA) is a non-coding RNA with longer than 200 nucleotides. Although a number of lncRNAs are highly expressed in the nervous system, their involvement in neuronal diseases is still poorly understood. Here, we report a role of the lncRNA Neat1 in the primary sensory neurons after nerve injury. The lumbar fifth spinal nerve ligation was performed in rats and pain behaviors were observed after the ligation. RNA sequencing was performed using polyadenylated RNA library from the dorsal root ganglion (DRG), where the cell bodies of primary sensory neurons are located. Among differentially expressed lncRNAs in the DRG 14 days after nerve injury, Neat1 represented a high basal expression level and the expression level was further increased after nerve injury. In situ hybridization revealed that Neat1 was mainly localized in the nucleus of primary sensory neurons. Both small and large cell-sized neurons expressed Neat1, whose distribution was unaffected by nerve injury. The knockdown of Neat1 expression by injection of adeno-associated viral vector encoding short-hairpin RNA for Neat1 into the DRG alleviated mechanical allodynia after nerve injury. On the other hand, the neurite outgrowth of primary sensory neurons was enhanced by Neat1 knockdown in vitro. RNA sequencing showed that Neat1 knockdown blocked the expression changes of many genes in the DRG after nerve injury, including genes involved in various neuronal functions and inflammatory processes. Therefore, Neat1 may serve as a multifunctional regulator for responses to nerve injury.
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