A Novel, Multi-Faceted Perception of Lactate in Neurology

Résumé

Lactate has become one of the most re-evaluated metabolites in energy metabolism, particularly \nas a shuttle in neuroenergetics (Mason, 2017; Ferguson et al., 2018). In a comprehensive review \nin 2018, Brooks, one of the originators of the “lactate shuttle” concept, discusses the roles that \nlactate plays in the delivery of oxidative, and gluconeogenic substrates, as well as in cell signaling \n(Brooks, 2018). Brooks also appraises clinical studies that feature lactate to treat pro-inflammatory \nconditions, as well as reports on historic and recent studies of lactate metabolism and shuttling. \nA pioneering astrocyte–neuron lactate shuttle (ANLS) hypothesis was first proposed in 1994 by \nPellerin and Magistretti for homeostatic conditions within the brain (Pellerin and Magistretti, \n1994). The ANLS hypothesis has withstood challenges for 25 years but remains controversial \nas scientists continue to debate its validity (Bak and Walls, 2018; Barros and Weber, 2018). I \nbelieve, however, that the ANLS hypothesis can be extended beyond homeostatic conditions into \nneuropathophysiological states. The focus of this short opinion paper is to highlight studies over \nthe past 2 years that support the notion that the route of lactate, as it acts as a shuttle in the \nbrain, in neuropathophysiological states is emerging as crucial in neuroenergetics. This behavior is \nreviewed in more detail by Mason (2017). Further, this paper presents recent experimental evidence \nthat has emerged supporting an extension of the ANLS—the newly postulated astrocyte–microglia \nlactate shuttle (AMLS) hypothesis (Mason et al., 2015), as described for the infectious, chronic \nneuroinflammatory disease tuberculous meningitis (TBM)

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