Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end-plate innervation.,Glia

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Disrupted function of lactate transporter MCT1, but not MCT4, in Schwann cells affects the maintenance of motor end-plate innervation.
Glia ( IF 5.4 ) Pub Date : 2020-07-20 , DOI: 10.1002/glia.23889
Filipa Bouçanova _{1,

2} , Gill Pollmeier ₁ , Katalin Sandor ₃ , Carlos Morado Urbina ₃ , Jik Nijssen ₁ , Jean-Jacques Médard _{1,

2} , Luca Bartesaghi _{1,

2} , Luc Pellerin _{4,

5,

6} , Camilla I Svensson ₃ , Eva Hedlund ₁ , Roman Chrast _{1,

2}

Affiliation

Recent studies in neuron‐glial metabolic coupling have shown that, in the CNS, astrocytes and oligodendrocytes support neurons with energy‐rich lactate/pyruvate via monocarboxylate transporters (MCTs). The presence of such transporters in the PNS, in both Schwann cells and neurons, has prompted us to question if a similar interaction may be present. Here we describe the generation and characterization of conditional knockout mouse models where MCT1 or MCT4 is specifically deleted in Schwann cells (named MCT1 and MCT4 cKO). We show that MCT1 cKO and MCT4 cKO mice develop normally and that myelin in the PNS is preserved. However, MCT1 expressed by Schwann cells is necessary for long‐term maintenance of motor end‐plate integrity as revealed by disrupted neuromuscular innervation in mutant mice, while MCT4 appears largely dispensable for the support of motor neurons. Concomitant to detected structural alterations, lumbar motor neurons from MCT1 cKO mice show transcriptional changes affecting cytoskeletal components, transcriptional regulators, and mitochondria related transcripts, among others. Together, our data indicate that MCT1 plays a role in Schwann cell‐mediated maintenance of motor end‐plate innervation thus providing further insight into the emerging picture of the biology of the axon‐glia metabolic crosstalk.

中文翻译：

雪旺细胞中乳酸转运蛋白 MCT1 而不是 MCT4 的功能紊乱会影响运动终板神经支配的维持。

最近对神经元-胶质细胞代谢偶联的研究表明，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蛋白 (MCT) 支持具有富含能量的乳酸/丙酮酸的神经元。在 PNS 中，在雪旺细胞和神经元中都存在这种转运蛋白，这促使我们质疑是否可能存在类似的相互作用。在这里，我们描述了条件性敲除小鼠模型的生成和表征，其中 MCT1 或 MCT4 在雪旺细胞中被特异性删除（称为 MCT1 和 MCT4 cKO）。我们显示 MCT1 cKO 和 MCT4 cKO 小鼠发育正常，并且 PNS 中的髓鞘得以保留。然而，雪旺细胞表达的 MCT1 是长期维持运动终板完整性所必需的，正如突变小鼠的神经肌肉神经支配被破坏所揭示的那样，而 MCT4 似乎在很大程度上对运动神经元的支持是可有可无的。伴随检测到的结构改变，来自 MCT1 cKO 小鼠的腰椎运动神经元显示出影响细胞骨架成分、转录调节因子和线粒体相关转录物等的转录变化。总之，我们的数据表明 MCT1 在雪旺细胞介导的运动终板神经支配维持中发挥作用，从而进一步深入了解轴突-胶质细胞代谢串扰的生物学新图景。

更新日期：2020-07-20

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