Glia-neuron energy metabolism in health and diseases: New insights into the role of nervous system metabolic transporters

Abstract

The brain is, by weight, only 2% the volume of the body and yet it consumes about 20% of the total glucose, suggesting that the energy requirements of the brain are high and that glucose is the primary energy source for the nervous system. Due to this dependence on glucose, brain physiology critically depends on the tight regulation of glucose transport and its metabolism. Glucose transporters ensure efficient glucose uptake by neural cells and contribute to the physiology and pathology of the nervous system. Despite this, a growing body of evidence demonstrates that for the maintenance of several neuronal functions, lactate, rather than glucose, is the preferred energy metabolite in the nervous system. Monocarboxylate transporters play a crucial role in providing metabolic support to axons by functioning as the principal transporters for lactate in the nervous system. Monocarboxylate transporters are also critical for axonal myelination and regeneration. Most importantly, recent studies have demonstrated the central role of glial cells in brain energy metabolism. A close and regulated metabolic conversation between neurons and both astrocytes and oligodendroglia in the central nervous system, or Schwann cells in the peripheral nervous system, has recently been shown to be an important determinant of the metabolism and function of the nervous system. This article reviews the current understanding of the long existing controversies regarding energy substrate and utilization in the nervous system and discusses the role of metabolic transporters in health and diseases of the nervous system.

Monocarboxylate transporter 1 in Schwann cells contributes to maintenance of sensory nerve myelination during aging

“…SC metabolism is critical for the regulation and maintenance of peripheral nerve development and function, and SCs are the primary cell type that metabolically support PNS axons (Beirowski et al, ; Jha & Morrison, ). Emerging evidence documents a close and regulated metabolic interaction between SCs and neurons in the PNS (Fields, ; Jha & Morrison, ).…”

“…SC metabolism is critical for the regulation and maintenance of peripheral nerve development and function, and SCs are the primary cell type that metabolically support PNS axons (Beirowski et al, ; Jha & Morrison, ). Emerging evidence documents a close and regulated metabolic interaction between SCs and neurons in the PNS (Fields, ; Jha & Morrison, ). GLUTs in endothelial cells (Froehner, Davies, Baldwin, & Lienhard, ), perineurial cells (Gerhart & Drewes, ; Takebe et al, ), and SCs (Magnani et al, ) facilitate the uptake of circulating glucose into SCs that can be metabolized to pyruvate, lactate, and other energy intermediates.…”

“…(Beirowski et al, 2014;Jha & Morrison, 2018). Emerging evidence documents a close and regulated metabolic interaction between SCs and neurons in the PNS (Fields, 2015;Jha & Morrison, 2018). GLUTs in endothelial cells (Froehner, Davies, Baldwin, & Lienhard, 1988), perineurial cells (Gerhart & Drewes, 1990;Takebe et al, 2008), and SCs (Magnani et al, 1996) (Jessen & Mirsky, 2008).…”

“…Mean ± SEM, n = 9 for wild-type and 6 for P0-cMCT1 KO groups, **p < .01; ns = not significant, unpaired t test. (Beirowski et al, 2014;Jha & Morrison, 2018). Emerging evidence documents a close and regulated metabolic interaction between SCs and neurons in the PNS (Fields, 2015;Jha & Morrison, 2018).…”

Monocarboxylate transporter 1 in Schwann cells is critical for maintenance of sensory nerve myelination during aging

“…Growing evidence suggests a critical role of lactate as a dynamic metabolite in health and diseases of peripheral nerves (Beirowski et al, 2014;Jha & Morrison, 2018). During catabolic processes, glycogen present in SCs is metabolized into lactate that may be transported to axons via monocarboxylate transporters (MCTs), which are bi-directional transporters of protons and monocarboxylates, including lactate, across plasma membranes.…”