Rapamycin Accelerates Axon Regeneration Through Schwann Cell-mediated Autophagy Following Inferior Alveolar Nerve Transection in Rats
Rapamycin Accelerates Axon Regeneration Through Schwann Cell-mediated Autophagy Following Inferior Alveolar Nerve Transection in Rats
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DOI：
10.1016/j.neuroscience.2021.05.033
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发表时间：
2021-06-18
期刊：
影响因子：
3.3
通讯作者：
Shinoda, Masamichi
中科院分区：
文献类型：
--
作者：
Inada, Takanobu;Sato, Hitoshi;Shinoda, Masamichi
由于三叉神经损伤而导致口面部区域的紊乱是由牙科治疗或事故引起的。市售疗法对于感觉障碍的治疗无效。此外，雷帕霉素（一种哺乳动物雷帕霉素靶标（mTOR）的变构抑制剂，负向调节自噬）对感觉障碍的治疗作用尚未得到充分研究。因此，我们研究了雷帕霉素对大鼠下牙槽神经（IAN）横断（IANX）引起的下颌区感觉障碍的治疗作用。通过向损伤部位施用雷帕霉素，横断的 IAN 近端和远端残端中磷酸化 p70S6K（mTOR 的下游分子）的表达水平显着降低。相反，雷帕霉素给药诱导横切 IAN 近端和远端残端中 Beclin 1 和微管相关蛋白 1 轻链 3-II 蛋白水平的增加。免疫组织化学分析显示 Beclin 1 位于 IAN 近端残端的雪旺细胞中。雷帕霉素给药显着减少了 IAN 近端和远端残端中髓磷脂零蛋白和髓磷脂碱性蛋白的积累。雷帕霉素的施用促进了 IANX 后的轴突再生，并增加了三叉神经节中脑源性神经营养因子阳性神经元的数量。因此，雷帕霉素显着促进了 IANX 引起的下唇感觉障碍的恢复。这些发现表明，雷帕霉素给药是治疗 IANX 引起的感觉障碍的一种有前途的治疗方法。 (c) 2021 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
disturbance in the orofacial region owing to trigeminal nerve injury is caused by dental treatment or accident. Commercially available therapeutics are ineffective for the treatment of sensory disturbance. Additionally, the therapeutic effects of rapamycin, an allosteric inhibitor of mammalian target of rapamycin (mTOR), which negatively regulates autophagy, on the sensory disturbance are not fully investigated. Thus, we investigated the therapeutic effects of rapamycin on the sensory disturbance in the mandibular region caused by inferior alveolar nerve (IAN) transection (IANX) in rats. The expression levels of the phosphorylated p70S6K, a downstream molecule of mTOR, in the proximal and distal stumps of the transected IAN were significantly reduced by rapamycin administration to the injured site. Conversely, the increments of both Beclin 1 and microtubule-associated protein-1 light chain 3-II protein levels in the proximal and distal stumps of the transected IAN was induced by rapamycin administration. Immunohistochemical analyses revealed that Beclin 1 was located in Schwann cells in the proximal stump of the IAN. Accumulation of myelin protein zero and myelin basic protein in the proximal and distal stumps of the IAN was significantly reduced by rapamycin administration. Rapamycin administration facilitated axon regeneration after IANX and increased the number of brain-derived neurotrophic factor positive neurons in the trigeminal ganglion. Thus, recovery from sensory disturbance in the lower lip caused by IANX was markedly facilitated by rapamycin. These findings suggest that rapamycin administration is a promising treatment for the sensory disturbance caused by IANX. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.