Domènech-Estévez Enric, Baloui Hasna, Repond Cendrine, Rosafio Katia, Médard Jean-Jacques, Tricaud Nicolas, Pellerin Luc, Chrast Roman
Departments of Medical Genetics and.
Physiology, University of Lausanne, Lausanne, CH-1005 Switzerland.
J Neurosci. 2015 Mar 11;35(10):4151-6. doi: 10.1523/JNEUROSCI.3534-14.2015.
Lactate, a product of glycolysis, has been shown to play a key role in the metabolic support of neurons/axons in the CNS by both astrocytes and oligodendrocytes through monocarboxylate transporters (MCTs). Despite such importance in the CNS, little is known about MCT expression and lactate function in the PNS. Here we show that mouse MCT1, MCT2, and MCT4 are expressed in the PNS. While DRG neurons express MCT1, myelinating Schwann cells (SCs) coexpress MCT1 and MCT4 in a domain-specific fashion, mainly in regions of noncompact myelin. Interestingly, SC-specific downregulation of MCT1 expression in rat neuron/SC cocultures led to increased myelination, while its downregulation in neurons resulted in a decreased amount of neurofilament. Finally, pure rat SCs grown in the presence of lactate exhibited an increase in the level of expression of the main myelin regulator gene Krox20/Egr2 and the myelin gene P0. These data indicate that lactate homeostasis participates in the regulation of the SC myelination program and reveal that similar to CNS, PNS axon-glial metabolic interactions are most likely mediated by MCTs.
乳酸是糖酵解的产物,已被证明在中枢神经系统中,星形胶质细胞和少突胶质细胞通过单羧酸转运体(MCTs)在神经元/轴突的代谢支持中发挥关键作用。尽管在中枢神经系统中具有如此重要性,但关于外周神经系统中MCT的表达和乳酸功能却知之甚少。在此我们表明,小鼠的MCT1、MCT2和MCT4在外周神经系统中表达。背根神经节(DRG)神经元表达MCT1,而形成髓鞘的施万细胞(SCs)以区域特异性方式共表达MCT1和MCT4,主要在非致密髓鞘区域。有趣的是,在大鼠神经元/施万细胞共培养物中,施万细胞特异性下调MCT1表达导致髓鞘形成增加,而在神经元中下调MCT1表达则导致神经丝数量减少。最后,在乳酸存在下培养的纯大鼠施万细胞表现出主要髓鞘调节基因Krox20/Egr2和髓鞘基因P0的表达水平增加。这些数据表明乳酸稳态参与施万细胞髓鞘形成程序的调节,并揭示与中枢神经系统类似,外周神经系统轴突-胶质细胞的代谢相互作用很可能由MCT介导。