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首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Ghrelin Protects Spinal Cord Motoneurons Against Chronic Glutamate Excitotoxicity by Inhibiting Microglial Activation
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Ghrelin Protects Spinal Cord Motoneurons Against Chronic Glutamate Excitotoxicity by Inhibiting Microglial Activation

机译：Ghrelin通过抑制小胶质细胞活化来保护脊髓神经元免受慢性谷氨酸兴奋性中毒。

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Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-3β pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia-deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.
机译：谷氨酸兴奋性毒性正在引起肌萎缩性侧索硬化症（ALS）中的脊髓运动神经元变性。最近，我们报道了生长素释放肽通过激活细胞外信号调节激酶1/2和磷脂酰肌醇3-激酶/ Akt /糖原合酶激酶3β途径来保护运动神经元免受慢性谷氨酸兴奋性中毒。先前的研究表明，激活的小胶质细胞活跃地参与了ALS运动神经元变性的发病机理。然而，仍然不知道ghrelin是否通过抑制小胶质细胞活化而对运动神经元发挥保护作用。在这项研究中，我们调查暴露于苏门冬氨酸（THA）的器官型脊髓培养物（OSCC），作为兴奋毒性运动神经元变性的模型，以确定生长素释放肽是否能阻止小胶质细胞活化。如先前报道，将OSCC暴露于THA 3周会导致典型的运动神经元死亡，而生长激素释放肽的治疗显着减弱了THA诱导的运动神经元丢失。 Ghrelin阻止THA诱导的脊髓小胶质细胞活化以及促炎细胞因子肿瘤坏死因子-α和白介素-1β的表达。我们的数据表明，ghrelin可能通过充当小胶质细胞失活因子而充当运动神经元的生存因子，并表明ghrelin可能具有治疗ALS和其他炎症反应起关键作用的神经退行性疾病的治疗潜力。

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