Lactate Transporters Mediate Glia-Neuron Metabolic Crosstalk in Homeostasis and Disease

Abstract

Research over the last couple of decades has provided novel insights into lactate neurobiology and the implications of lactate transport-driven neuroenergetics in health and diseases of peripheral nerve and the brain. The expression pattern of lactate transporters in glia and neurons has now been described, though notable controversies and discrepancies remain. Importantly, down- and up-regulation experiments are underway to better understand the function of these transporters in different systems. Lactate transporters in peripheral nerves are important for maintenance of axon and myelin integrity, motor end-plate integrity, the development of diabetic peripheral neuropathy (DPN), and the functional recovery following nerve injuries. Similarly, brain energy metabolism and functions ranging from development to synaptic plasticity to axonal integrity are also dependent on lactate transport primarily between glia and neurons. This review is focused on critically analysing the expression pattern and the functions of lactate transporters in peripheral nerves and the brain and highlighting their role in glia-neuron metabolic crosstalk in physiological and pathological conditions.

Río‐Hortega's drawings revisited with fluorescent protein defines a cytoplasm‐filled channel system of CNS myelin

“…The second being the observation that oligodendrocytes supply energy‐rich metabolites to axons (Fünfschilling et al, 2012 ; Lee et al, 2012 ), presumably reaching the axon by way of the myelinic channel system (Saab et al, 2013 ). Indeed, the recent observation that CNP contributes to keeping the cytoplasmic channels of myelin open (Snaidero et al, 2017 ) raises the possibility that secondary axon degeneration (and inner tongue swelling) in the Cnp1 knockout mouse reflects collapse of the myelinic channel system and impaired trafficking of glial‐derived materials such as monocarboxylate transporters (Jha & Morrison, 2020 ; Lee et al, 2012 ) and metabolites to the glial–axonal junction, as speculated (Edgar et al, 2009 ; Nave, 2010 ). Finally, the adaxonal cytoplasmic compartment of the myelin sheath also contributes to the electric currents during saltatory impulse conduction (Cohen et al, 2020 ).…”

Monocarboxylate Transporter 1 May Benefit Cerebral Ischemia via Facilitating Lactate Transport From Glial Cells to Neurons

“…Research over the last couple of decades has provided novel insights into lactate neurobiology and the implications of lactate transport-driven neuroenergetics in the health and diseases of peripheral nerve and CNS. Lactate transporters in peripheral nerves are important for the maintenance of axon and myelin integrity, motor end-plate integrity, the development of diabetic peripheral neuropathy (DPN), and the functional recovery following nerve injuries ( 99 ). This review discusses that the regulation of MCT1 in ANSL and oligodendrocyte-neuron lactate flow are necessary for the functional recovery of neurons under I/R injury.…”

Release of VAMP5-positive extracellular vesicles by retinal Müller gliain vivo

“…Glial cells control the development (Araujo et al, 2019;Lago-Baldaia et al, 2020;Tan et al, 2021) and function (García-Cáceres et al, 2019;Kofuji and Araque, 2021;Nave and Werner, 2021) of neurons and they influence the outcome of pathologic conditions due to disease or injury (Kim et al, 2020;Linnerbauer et al, 2020;Patel et al, 2019;Raiders et al, 2021;Wilton et al, 2019;Wilton and Stevens, 2020). During the last years, much has been learned Demais et al Extracellular vesicles from retinal Müller cells 3 about glia-neuron interactions: neurons and different types of glial cells communicate via intercellular contacts and via the release of molecules fulfilling multiple functions that range from structural, energy and trophic support to cell signaling (Giaume et al, 2021;Hillen et al, 2018;Illes et al, 2019;Jha and Morrison, 2020;Seifert and Steinhäuser, 2018;Shen et al, 2017;Sultan et al, 2015). Molecules of the secretome that are contained in intracellular vesicles can be released directly into the extracellular space following fusion of the vesicular membrane with the plasma membrane (Fiacco and McCarthy, 2018;Murat and García-Cáceres, 2021;Savtchouk and Volterra, 2018;Vardjan et al, 2019).…”