There is accumulating, convincing experimental evidence that glial cells play a key role in regulating the energy homeostasis of the nervous system, with disruption to glial cell metabolism associated with numerous disparate pathological conditions. The majority of this research has focused on astrocytes of the central nervous system (CNS). A key aspect of astrocyte physiology is their expression of glycogen, which is metabolised to lactate for distribution to neighbouring neurones/axons. Despite being versatile cells, performing myriad functions, astrocytes comprise only one type of glial cell in the CNS, another notable glial cell being the oligodendrocyte, which myelinates axons, a role assumed by Schwann cells in the peripheral nervous system (PNS). Similarities and differences exist in the metabolic role performed by these myelinating glial cells. Briefly, Schwann cells are the source of glycogen in the PNS, but only those Schwann cells myelinating A fibres provide metabolic support to axons. Specialised Schwann cells called Remak cells which ensheathe C fibres provide these axons with no metabolic support. The role of glial cells as suppliers of metabolic substrates to neural elements implies a messaging system whereby the metabolic needs of the neural elements are rapidly and efficiently conveyed to the glial cells. The first metabolic signal proposed was glutamate as part of the Astrocyte-Neurone Lactate Shuttle Hypothesis (ANLSH). Recent research has suggested the ability of both myelinating glial cells to respond to glutamate, with a particular focus on the oligodendrocytes, which respond to glutamate as a metabolic signal as part of the axo-myelinic synapse. This is an exciting area of research with knowledge of the metabolic role of myelinating glia providing potential future insight into the importance of their metabolic role in myelin formation and maintenance, as well as pathological conditions including diabetes and multiple sclerosis.
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