From rags to riches: Lactate ascension as a pivotal metabolite in neuroenergetics

Schurr, Avital

doi:10.3389/fnins.2023.1145358

Cited by 3 publications

(2 citation statements)

References 51 publications

(51 reference statements)

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“…It is produced intracellularly with NAD + via glycolysis and exists in equilibrium with the redox couple pyruvate and NADH [ 44 ]. Long thought of as a dead-end waste product produced in response to hypoxia, it is now considered to be the obligatory end-product of glycolysis and a crucial substrate that fuels mitochondrial bioenergetics [ 43 ]. Lactate is enriched around mitochondria with concentrations in the range of ~268–1025 µM (<100 µM in the nucleus/cytosol) [ 52 ].…”

Section: Lactate Neurophysiologymentioning

confidence: 99%

“…This prompted the ‘lactate hypothesis of anxiety’ and the characterisation of exogenous sodium lactate as a panicogenic agent [ 41 ]. More recently, lactate has also been purported to have antidepressant properties [ 42 ], and the field has received much attention with lactate going from ‘from rags to riches’ [ 43 ], once ‘the ugly duckling of metabolism’ [ 44 ], now ‘a phoenix risen’ [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

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Lactate: A Theranostic Biomarker for Metabolic Psychiatry?

Caddye,

Pineau,

Reyniers

et al. 2023

Antioxidants

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Alterations in neurometabolism and mitochondria are implicated in the pathophysiology of psychiatric conditions such as mood disorders and schizophrenia. Thus, developing objective biomarkers related to brain mitochondrial function is crucial for the development of interventions, such as central nervous system penetrating agents that target brain health. Lactate, a major circulatory fuel source that can be produced and utilized by the brain and body, is presented as a theranostic biomarker for neurometabolic dysfunction in psychiatric conditions. This concept is based on three key properties of lactate that make it an intriguing metabolic intermediate with implications for this field: Firstly, the lactate response to various stimuli, including physiological or psychological stress, represents a quantifiable and dynamic marker that reflects metabolic and mitochondrial health. Second, lactate concentration in the brain is tightly regulated according to the sleep–wake cycle, the dysregulation of which is implicated in both metabolic and mood disorders. Third, lactate universally integrates arousal behaviours, pH, cellular metabolism, redox states, oxidative stress, and inflammation, and can signal and encode this information via intra- and extracellular pathways in the brain. In this review, we expand on the above properties of lactate and discuss the methodological developments and rationale for the use of functional magnetic resonance spectroscopy for in vivo monitoring of brain lactate. We conclude that accurate and dynamic assessment of brain lactate responses might contribute to the development of novel and personalized therapies that improve mitochondrial health in psychiatric disorders and other conditions associated with neurometabolic dysfunction.

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Section: Lactate Neurophysiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lactate: A Theranostic Biomarker for Metabolic Psychiatry?

Caddye,

Pineau,

Reyniers

et al. 2023

Antioxidants

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Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation

Morelli,

Scholkmann

2024

Biochimie

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How the ‘Aerobic/Anaerobic Glycolysis’ Meme Formed a ‘Habit of Mind’ Which Impedes Progress in the Field of Brain Energy Metabolism

Schurr

2024

IJMS

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The division of glycolysis into two separate pathways, aerobic and anaerobic, depending on the presence or absence of oxygen, respectively, was formulated over eight decades ago. The former ends with pyruvate, while the latter ends with lactate. Today, this division is confusing and misleading as research over the past 35 years clearly has demonstrated that glycolysis ends with lactate not only in cancerous cells but also in healthy tissues and cells. The present essay offers a review of the history of said division and the more recent knowledge that has been gained about glycolysis and its end-product, lactate. Then, it presents arguments in an attempt to explain why separating glycolysis into aerobic and anaerobic pathways persists among scientists, clinicians and teachers alike, despite convincing evidence that such division is not only wrong scientifically but also hinders progress in the field of energy metabolism.

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From rags to riches: Lactate ascension as a pivotal metabolite in neuroenergetics

Cited by 3 publications

References 51 publications

Lactate: A Theranostic Biomarker for Metabolic Psychiatry?

Lactate: A Theranostic Biomarker for Metabolic Psychiatry?

Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation

How the ‘Aerobic/Anaerobic Glycolysis’ Meme Formed a ‘Habit of Mind’ Which Impedes Progress in the Field of Brain Energy Metabolism

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