Finsterwald Charles, Dias Sara, Magistretti Pierre J, Lengacher Sylvain
GliaPharm SA, Geneva, Switzerland.
Front Pharmacol. 2021 Apr 28;12:653842. doi: 10.3389/fphar.2021.653842. eCollection 2021.
Gangliosides are major constituents of the plasma membrane and are known to promote a number of physiological actions in the brain, including synaptic plasticity and neuroprotection. In particular, the ganglioside GM1 was found to have a wide range of preclinical and clinical benefits in brain diseases such as spinal cord injury, Huntington's disease and Parkinson's disease. However, little is known about the underlying cellular and molecular mechanisms of GM1 in the brain. In the present study, we show that GM1 exerts its actions through the promotion of glycolysis in astrocytes, which leads to glucose uptake and lactate release by these cells. In astrocytes, GM1 stimulates the expression of several genes involved in the regulation of glucose metabolism. GM1 also enhances neuronal mitochondrial activity and triggers the expression of neuroprotection genes when neurons are cultured in the presence of astrocytes. Finally, GM1 leads to a neuroprotective effect in astrocyte-neuron co-culture. Together, these data identify a previously unrecognized mechanism mediated by astrocytes by which GM1 exerts its metabolic and neuroprotective effects.
神经节苷脂是质膜的主要成分，已知其可促进大脑中的多种生理活动，包括突触可塑性和神经保护作用。特别是，神经节苷脂GM1在脊髓损伤、亨廷顿舞蹈症和帕金森病等脑部疾病中具有广泛的临床前和临床益处。然而，关于GM1在大脑中的潜在细胞和分子机制知之甚少。在本研究中，我们表明GM1通过促进星形胶质细胞的糖酵解发挥作用，这导致这些细胞摄取葡萄糖并释放乳酸。在星形胶质细胞中，GM1刺激参与葡萄糖代谢调节的几个基因的表达。当神经元在星形胶质细胞存在的情况下培养时，GM1还增强神经元线粒体活性并触发神经保护基因的表达。最后，GM1在星形胶质细胞-神经元共培养中产生神经保护作用。总之，这些数据确定了一种由星形胶质细胞介导的先前未被认识的机制，通过该机制GM1发挥其代谢和神经保护作用。
