德国马克斯普朗克多学科科学研究所Klaus-Armin Nave、Ebrahim Asadollahi研究组取得一项新突破。他们发现少突胶质细胞中的脂肪酸代谢为中枢神经系统提供储备能量。这一研究成果发表在2024年9月9日出版的国际学术期刊《自然— 神经科学》上。

研究人员发现少突胶质细胞中持续的脂质代谢为白质束提供了能量储备。在离体的成年雌雄小鼠视神经中，少突胶质细胞比星形胶质细胞更能在葡萄糖剥夺条件下存活。在低葡萄糖时，轴突的ATP水平和动作电位都依赖于脂肪酸的β-氧化。

重要的是，持续的少突胶质细胞脂质降解会迅速影响白质的能量代谢。线粒体和少突胶质细胞过氧化物酶体中的脂肪酸β-氧化，虽然不能支持高频尖峰脉冲，但却能在葡萄糖受限时保护轴突免受传导阻滞。

成年小鼠少突胶质细胞中葡萄糖转运体GLUT1的表达中断，会扰乱体内髓鞘的稳态，并导致由逐渐脱髓鞘引起的无行为症状。该研究进一步表明，髓鞘合成和降解的失衡可能是衰老和疾病诱导髓鞘变薄的原因。

据介绍，大脑发挥正常功能需要持续的葡萄糖供给。然而，除了星形胶质细胞中的糖原颗粒外，大脑没有其他已知的储备能量。

附：英文原文

Title: Oligodendroglial fatty acid metabolism as a central nervous system energy reserve

Author: Asadollahi, Ebrahim, Trevisiol, Andrea, Saab, Aiman S., Looser, Zoe J., Dibaj, Payam, Ebrahimi, Reyhane, Kusch, Kathrin, Ruhwedel, Torben, Mbius, Wiebke, Jahn, Olaf, Lee, Jun Yup, Don, Anthony S., Khalil, Michelle-Amirah, Hiller, Karsten, Baes, Myriam, Weber, Bruno, Abel, E. Dale, Balabio, Andrea, Popko, Brian, Kassmann, Celia M., Ehrenreich, Hannelore, Hirrlinger, Johannes, Nave, Klaus-Armin

Issue&Volume: 2024-09-09

Abstract: Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial peroxisomes protects axons from conduction blocks when glucose is limiting. Disruption of the glucose transporter GLUT1 expression in oligodendrocytes of adult mice perturbs myelin homeostasis in vivo and causes gradual demyelination without behavioral signs. This further suggests that the imbalance of myelin synthesis and degradation can underlie myelin thinning in aging and disease.

DOI: 10.1038/s41593-024-01749-6

Source: https://www.nature.com/articles/s41593-024-01749-6