Spine Disease Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Neurochem. 2020 Sep;155(2):154-176. doi: 10.1111/jnc.15011. Epub 2020 Apr 13.
Cervical spondylotic myelopathy (CSM) is a common cause of disability with few treatments. Aberrant mitochondrial dynamics play a crucial role in the pathogenesis of various neurodegenerative diseases. Thus, regulation of mitochondrial dynamics may offer therapeutic benefit for the treatment of CSM. Muscone, the active ingredient of an odoriferous animal product, exhibits anti-inflammatory and neuroprotective effects for which the underlying mechanisms remain obscure. We hypothesized that muscone might ameliorate inflammatory responses and neuronal damage by regulating mitochondrial dynamics. To this end, the effects of muscone on a rat model of chronic cervical cord compression, as well as activated BV2 cells and injured neurons, were assessed. The results showed that muscone intervention improved motor function compared with vehicle-treated rats. Indeed, muscone attenuated pro-inflammatory cytokine expression, neuronal-apoptosis indicators in the lesion area, and activation of the nod-like receptor family pyrin domain-containing 3 inflammasome, nuclear transcription factor-κB, and dynamin-related protein 1 in Iba1- and βIII-tubulin-labeled cells. Compared with vehicle-treated rats, compression sites of muscone-treated animals exhibited elongated mitochondrial morphologies in individual cell types and reduced reactive oxygen species. In vitro results indicated that muscone suppressed microglial activation and neuronal damage by regulating related-inflammatory or apoptotic molecules. Moreover, muscone inhibited dynamin-related protein 1 activation in activated BV2 cells and injured neurons, whereby it rescued mitochondrial fragmentation and reactive oxygen species production, which regulate a wide range of inflammatory and apoptotic molecules. Our findings reveal that muscone attenuates neuroinflammation and neuronal damage in rats with chronic cervical cord compression by regulating mitochondrial fission events, suggesting its promise for CSM therapy.
脊髓型颈椎病（CSM）是一种常见的致残原因，治疗方法很少。异常的线粒体动力学在各种神经退行性疾病的发病机制中起着关键作用。因此，调节线粒体动力学可能为 CSM 的治疗提供治疗益处。麝香酮是一种有气味的动物产品的活性成分，具有抗炎和神经保护作用，但其潜在机制尚不清楚。我们假设麝香酮可能通过调节线粒体动力学来改善炎症反应和神经元损伤。为此，评估了麝香酮对慢性颈脊髓压迫大鼠模型以及激活的 BV2 细胞和损伤神经元的影响。结果表明，与载体处理的大鼠相比，麝香酮干预改善了运动功能。事实上，麝香酮减弱了病变区域促炎细胞因子表达、神经元凋亡标志物以及 NOD 样受体家族吡喃结构域包含 3 炎性小体、核转录因子-κB 和动力相关蛋白 1 在 Iba1 和 βIII-微管蛋白标记细胞中的激活。与载体处理的大鼠相比，麝香酮处理动物的压缩部位在单个细胞类型中表现出延长的线粒体形态，并且活性氧减少。体外结果表明，麝香酮通过调节相关炎症或凋亡分子来抑制小胶质细胞激活和神经元损伤。此外，麝香酮抑制激活的 BV2 细胞和损伤神经元中的动力相关蛋白 1 激活，从而挽救线粒体片段化和活性氧的产生，调节广泛的炎症和凋亡分子。我们的研究结果表明，麝香酮通过调节线粒体分裂事件减轻慢性颈脊髓压迫大鼠的神经炎症和神经元损伤，提示其在 CSM 治疗中的应用前景。
