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首页> 外文期刊>The European Journal of Neuroscience >Sphingosylphosphocholine effects on cultured astrocytes reveal mechanisms potentially involved in neurotoxicity in Niemann-Pick type A disease.
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Sphingosylphosphocholine effects on cultured astrocytes reveal mechanisms potentially involved in neurotoxicity in Niemann-Pick type A disease.

机译：鞘氨醇磷酸胆碱对培养的星形胶质细胞的作用揭示了可能与尼曼-匹克A型疾病的神经毒性有关的机制。

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摘要

Niemann-Pick type A is a disease characterized by the absence of a functional SMPD1 (acidic sphingomyelinase) gene and the abnormal accumulation of sphingomyelin. Under these conditions, also sphingosylphosphocholine (SPC, a sphingomyelin metabolite) accumulates in various tissues, including the brain, where it might act as a toxic stimulus, contributing to the appearance of the neurological symptoms. We studied the effects of SPC on astrocytic and neuronal cultures from rat. In particular, we investigated the possibility that SPC acts on astrocytes and that this represents the first step leading to neurodegeneration. Our results show that acute administration of SPC to astrocytes in culture promotes Ca2+ responses and a release of glutamate that, in turn, leads to cytosolic [Ca2+] elevation in neurons. We also show that chronic stimulation by SPC leads astrocytes to proliferate, but can also change their phenotype towards an activated state that might contribute to the inflammatory responses. Interestingly, upon acute SPC stimulation, activated astrocytes release more glutamate. In conclusion, we show that both chronic and acute exposure to SPC can constitute harmful signals that may have a role in the sequence of events leading to neurodegeneration.
机译：Niemann-Pick A型是一种以功能性SMPD1（酸性鞘磷脂酶）基因缺失和鞘磷脂异常蓄积为特征的疾病。在这种情况下，鞘氨醇磷酸胆碱（SPC，一种鞘磷脂代谢产物）也会积聚在包括大脑在内的各种组织中，在这些组织中，它可能起毒性刺激作用，有助于出现神经系统症状。我们研究了SPC对大鼠星形细胞和神经元文化的影响。特别是，我们研究了SPC作用于星形胶质细胞的可能性，这代表了导致神经变性的第一步。我们的结果表明，对培养物中的星形胶质细胞进行SPC急性给药可促进Ca2 +反应和谷氨酸的释放，进而导致神经元中胞质[Ca2 +]升高。我们还表明，SPC的慢性刺激会导致星形胶质细胞增生，但也可能将其表型改变为可能导致炎症反应的活化状态。有趣的是，在急性SPC刺激下，活化的星形胶质细胞释放更多的谷氨酸。总之，我们表明慢性和急性SPC暴露均可构成有害信号，这些信号可能在导致神经退行性变的事件序列中起作用。

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