Muscone通过调节依赖于Drp1的线粒体裂变来抑制颈椎病脊髓模型的炎症反应和神经元损伤,Journal of Neurochemistry

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Muscone通过调节依赖于Drp1的线粒体裂变来抑制颈椎病脊髓模型的炎症反应和神经元损伤
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2020-03-25 , DOI: 10.1111/jnc.15011
Long-yun Zhou _{1,

2,

3} , Min Yao _{1,

2} , Zi-rui Tian _{1,

2} , Shu-fen Liu _{1,

2} , Yong-jia Song _{1,

2} , Jie Ye ₄ , Gan Li _{1,

2} , Yue-li Sun _{1,

2} , Xue-jun Cui _{1,

2} , Yong-jun Wang _{1,

2}

Affiliation

颈椎病脊髓病（CSM）是导致残疾的常见原因，几乎没有治疗方法。异常的线粒体动力学在各种神经退行性疾病的发病机理中起着至关重要的作用。因此，调节线粒体动力学可能为CSM的治疗提供治疗益处。Muscone是有味动物产品的活性成分，具有抗发炎和神经保护作用，但其潜在机制仍不清楚。我们假设，muscone可能通过调节线粒体动力学改善炎症反应和神经元损伤。为此，评估了麝香酮对慢性宫颈脊髓压迫，活化的BV2细胞和受损神经元大鼠模型的影响。结果表明，与载体治疗的大鼠相比，麝香酮干预改善了运动功能。实际上，muscone减弱了病变区域的促炎性细胞因子表达，神经元凋亡指标，并激活了Iba1‐3中包含3个炎性小体，核转录因子κB和动力蛋白相关蛋白1的nod样受体家族的吡啶结构域的活化。和βIII-微管蛋白标记的细胞。与用媒介物处理的大鼠相比，用麝香酮处理的动物的压迫部位在单个细胞类型中表现出延长的线粒体形态，并减少了活性氧。体外实验结果表明，muscone通过调节相关的炎症或凋亡分子来抑制小胶质细胞活化和神经元损伤。此外，muscone抑制了活化的BV2细胞和受损神经元中与发电机相关的蛋白1的活化，从而挽救了线粒体的片段化和活性氧的产生，调节各种炎症和凋亡分子。我们的发现表明，muscone可通过调节线粒体裂变事件来减轻慢性宫颈压迫大鼠的神经炎症和神经元损伤，表明其有望用于CSM治疗。

"点击查看英文标题和摘要"

Muscone suppresses inflammatory responses and neuronal damage in a rat model of cervical spondylotic myelopathy by regulating Drp1‐dependent mitochondrial fission

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.

更新日期：2020-03-25

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