In several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore axonal ATP dynamics in the Plp^null/y mouse model of spastic paraplegia. Optic nerves from Plp^null/y mice exhibited lower and more variable basal axonal ATP levels and reduced compound action potential (CAP) amplitudes, providing a missing link between axonal pathology and a role of oligodendrocytes in brain energy metabolism. Surprisingly, when Plp^null/y optic nerves are challenged with transient glucose deprivation, both ATP levels and CAP decline slower, but recover faster upon reperfusion of glucose. Structurally, myelin sheaths display an increased frequency of cytosolic channels comprising glucose and monocarboxylate transporters, possibly facilitating accessibility of energy substrates to the axon. These data imply that complex metabolic alterations of the axon–myelin unit contribute to the phenotype of Plp^null/y mice.

在几种神经退行性疾病中，轴突病理可能源自能量底物的少突胶质细胞至轴突支持受损。我们先前建立了转基因小鼠，可以测量电活动性视神经中的轴突ATP水平。在这里，我们利用这项技术来探索痉挛性截瘫的Plp ^{null / y}小鼠模型中的轴突ATP动态。来自Plp ^{null / y}小鼠的视神经表现出更低和更多的基础轴突ATP水平，并降低了复合动作电位（CAP）幅度，从而在轴突病理与少突胶质细胞在脑能量代谢中的作用之间缺乏联系。令人惊讶的是，当Plp为^{null / y}短暂性葡萄糖缺乏会挑战视神经，ATP水平和CAP下降均较慢，但葡萄糖再灌注后恢复较快。在结构上，髓鞘显示出增加的频率的胞浆通道，包括葡萄糖和单羧酸盐转运蛋白，可能促进能量底物对轴突的可及性。这些数据表明，轴突－髓磷脂单元的复杂代谢改变有助于Plp ^{null / y}小鼠的表型。