School of Life Sciences, University of Nottingham, Nottingham, NG7 2UH, UK.
Department of Neurology, School of Medicine, University of Washington, Seattle, WA, 98195, USA.
J Physiol. 2018 May 15;596(10):1795-1812. doi: 10.1113/JP275680. Epub 2018 Apr 16.
We have developed an improved method that enables simultaneous recording of stimulus evoked compound action potentials from large myelinated A fibres and small unmyelinated C fibres in mouse sciatic nerves. Investigations into the ability of fructose to support conduction in sciatic nerve revealed a novel glia-to-axon metabolic pathway in which fructose is converted in Schwann cells to lactate for subsequent shuttling to A fibres. The C fibres most likely directly take up and metabolise fructose. These differences are indicative of fibre sub-type specific metabolic profiles. These results demonstrate that the physiological insights provided by the method can be applied to investigations of peripheral nerve, with a view to understanding the metabolic disruptions that underlie diabetic neuropathy.
The stimulus evoked compound action potential (CAP), recorded using suction electrodes, provides an index of the relative number of conducting axons within a nerve trunk. As such the CAP has been used to elucidate the diverse mechanisms of injury resulting from a variety of metabolic insults to central nervous white matter, whilst also providing a model with which to assess the benefits of clinically relevant neuroprotective strategies. In addition the technique lends itself to the study of metabolic cell-to-cell signalling that occurs between glial cells and neurones, and to exploring the ability of non-glucose substrates to support axon conduction. Although peripheral nerves are sensitive to metabolic insult and are susceptible to diabetic neuropathy, there is a lack of fundamental information regarding peripheral nerve metabolism. A confounding factor in such studies is the extended duration demanded by the experimental protocol, requiring stable recording for periods of many hours. We describe a method that allows us to record simultaneously the stimulus evoked CAPs from A and C fibres from mouse sciatic nerve, and demonstrate its utility as applied to investigations into fibre sub-type substrate use. Our results suggest that C fibres directly take up and metabolise fructose, whereas A fibre conduction is supported by fructose-derived lactate, implying there exist unique metabolic profiles in neighbouring fibre sub-types present within the same nerve trunk.
我们开发了一种改进的方法，能够同时记录小鼠坐骨神经中大有髓 A 纤维和小无髓 C 纤维的刺激诱发复合动作电位。对果糖支持坐骨神经传导能力的研究揭示了一种新的胶质细胞-轴突代谢途径，其中果糖在施万细胞中转化为乳酸，随后转运到 A 纤维。C 纤维很可能直接摄取和代谢果糖。这些差异表明纤维亚型具有特异性代谢特征。这些结果表明，该方法提供的生理学见解可应用于周围神经的研究，以期了解糖尿病神经病变中潜在的代谢紊乱。
刺激诱发复合动作电位（CAP），使用吸力电极记录，提供了神经干内传导轴突相对数量的指标。因此，CAP 被用于阐明中枢白质受到各种代谢损伤后的多种损伤机制，同时也为评估临床相关神经保护策略的益处提供了一种模型。此外，该技术适用于研究发生在胶质细胞和神经元之间的代谢细胞间信号传递，以及探索非葡萄糖底物支持轴突传导的能力。尽管周围神经对代谢损伤敏感，容易发生糖尿病神经病变，但关于周围神经代谢的基本信息却很缺乏。在这些研究中，一个混杂因素是实验方案所需的时间延长，需要稳定记录数小时。我们描述了一种能够同时记录小鼠坐骨神经 A 和 C 纤维刺激诱发 CAP 的方法，并展示了其在纤维亚型底物利用研究中的应用。我们的结果表明，C 纤维直接摄取和代谢果糖，而 A 纤维的传导则由果糖衍生的乳酸支持，这意味着在同一神经干内存在的相邻纤维亚型中存在独特的代谢特征。
