Lactate in the brain: from metabolic end-product to signalling molecule
Open accessAbstract
Lactate in the brain has long been associated with ischaemia; however, more recent evidence shows that it can be found there under physiological conditions. In the brain, lactate is formed predominantly in astrocytes from glucose or glycogen in response to neuronal activity signals. Thus, neurons and astrocytes show tight metabolic coupling. Lactate is transferred from astrocytes to neurons to match the neuronal energetic needs, and to provide signals that modulate neuronal functions, including excitability, plasticity and memory consolidation. In addition, lactate affects several homeostatic functions. Overall, lactate ensures adequate energy supply, modulates neuronal excitability levels and regulates adaptive functions in order to set the 'homeostatic tone' of the nervous system.
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Lactate is intimately associated with exercise adaptations in brain function, providing signals that modulate neuronal functions, including excitability, plasticity and memory consolidation.
“Lactate is also intimately associated with exercise adaptations in brain function, whereby it provides signals that modulate neuronal functions, including excitability, plasticity and memory consolidation [55].”
Lactate taken up by neurons is reconverted into pyruvate and utilized by mitochondria to generate ATP.
“Lactate taken up by neurons is reconverted into pyruvate and ultimately utilized by mitochondria to generate ATP.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [13]
Lactate produced in astrocytes can be released into extracellular space via MCTs and taken up by neurons through neuronal MCTs (ANLS).
“Lactate produced in astrocytes can be released into the extracellular space via monocarboxylate transporters (MCTs). This lactate is subsequently taken up by neurons through neuronal MCTs, a process known as the astrocyte–neuron lactate shuttle (ANLS)12,13.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [13]
Oligodendrocytes may be distinguished from astrocytes, which express LDH and reportedly use a lactate shuttle to directly support synaptic energy metabolism in cortical gray matter.
“This may distinguish oligodendrocytes from astrocytes that express LDH and reportedly use a”
From Downregulated expression of lactate dehydrogenase in adult oligodendrocytes and its implication for the transfer of glycolysis products to axons (2024) · cites this paper as Magistretti & Allaman, 2018
Neuron and astrocyte are coupled in glucose oxidation.
“As the two most abundant, and energetically most essential cell types in the brain, neuron and astrocyte are coupled in not only glucose oxidation (Magistretti and Allaman, 2018; Yellen, 2018), but also lipid metabolism (Barber and Raben, 2019).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Magistretti and Allaman, 2018
The capacity in performing glycolysis and OXPHOS varies between neurons and astrocytes.
“The capacity in performing glycolysis and OXPHOS varies between neuron and astrocyte (Magistretti and Allaman, 2018; Yellen, 2018).”
From ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism (2021) · cites this paper as Magistretti and Allaman, 2018
These mechanisms might work with a lower glucose threshold resulting in a higher risk of developing hypoglycemia unawareness syndrome.
“Consequently, these mechanisms might work with a lower glucose threshold resulting in a higher risk of developing hypoglycemia unawareness syndrome [ 10 , 18 , 20 ].”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [20]
Recent antecedent hypoglycemic episodes do not increase blood-to-brain glucose transport.
“However, recent antecedent hypoglycemic episodes do not increase these mechanisms with a higher blood-to-brain glucose transport.”
From Hypoglycemia Unawareness—A Review on Pathophysiology and Clinical Implications (2024) · cites this paper as [20]
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- Authors
- Magistretti, P. J., & Allaman, I.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Magistretti, Pierre J.
- Venue
- Nature Reviews Neuroscience
- Published
- 2018-03-08
- Volume
- 19
- Issue
- 4
- Pages
- 235-249
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- OpenAlex
- W2789730644
- Semantic Scholar
- 1adbd144fde8ee562f1b063b48afcc9ef2df47bb
- Cited by
- 1,298
- References
- 211
- Citations by year
- 2026: 209 · 2025: 201 · 2024: 210 · 2023: 178 · 2022: 147 · 2021: 144 · 2020: 104 · 2019: 68 · 2018: 34
- FWCI
- 11.33
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- IRIS (submittedVersion)
- King Abdullah University of Science and Technology Repository (King Abdullah University of Science and Technology) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- brain lactate, astrocytes, neuronal excitability, synaptic plasticity, memory consolidation, brain energy metabolism, lactate transport, ischemia
- MeSH terms
- Animals, Astrocytes, Brain, Energy Metabolism, Humans, Memory, Neuronal Plasticity, Neurons, Signal Transduction, Lactic Acid
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