ArticleProceedings of the National Academy of Sciences of the United States of America2015
NH4(+) triggers the release of astrocytic lactate via mitochondrial pyruvate shunting.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- Characterizing the metabolomes of microglia, astrocytes and neurons in ageing and Alzheimer's brains.Nature cell biology · 2026Article
- Astrocytic GPR55 receptors promote glycolysis.Journal of cannabis research · 2026Article
- ZBTB7A-mediated regulation of astrocytic glycolysis in neurodegenerative diseases: insights from literature review and bioinformatics prediction.Frontiers in aging neuroscience · 2026Review
- Hypothalamic Astrocytes Exhibit Glycolytic Features Making Them Prone for Glucose Sensing.Glia · 2025Article
- MGlu5 Dependent Mitochondrial Translocation of PKCδ: A Mechanism Raising Astrocytic Oxidative Metabolism in Response to Extracellular Glutamate.Journal of neurochemistry · 2025Article
- Two-point calibration protocol for the Förster Resonance Energy Transfer indicator Pyronic in neurons.Neurophotonics · 2025Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Dynamics of Neuronal and Astrocytic Energy Molecules in Epilepsy.Journal of neurochemistry · 2025Article
- Autophagy regulator ATG5 preserves cerebellar function by safeguarding its glycolytic activity.Nature metabolism · 2025Article
- The Astrocyte: Metabolic Hub of the Brain.Cold Spring Harbor perspectives in biology · 2024Review
- A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice.Nature communications · 2024Article
- Glycolysis-derived alanine from glia fuels neuronal mitochondria for memory in Drosophila.Nature metabolism · 2023Article
- Glial metabolism checkpoints memory.Nature metabolism · 2023Article
- Mapping between cognitive theories and psycho-physiological models of attention system performance.Cerebral cortex (New York, N.Y. : 1991) · 2023Review
- Understanding ayahuasca effects in major depressive disorder treatment through in vitro metabolomics and bioinformatics.Analytical and bioanalytical chemistry · 2023Article
- Astrocyte Molecular Clock Function in the Nucleus Accumbens Is Important for Reward-Related Behavior.Biological psychiatry · 2022Article
- KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- How expensive is the astrocyte?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- The Glial Cells Respond to Spinal Cord Injury.Frontiers in neurology · 2022Review
- GEM-IL: A highly responsive fluorescent lactate indicator.Cell reports methods · 2021Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neural activity is accompanied by a transient mismatch between local glucose and oxygen metabolism, a phenomenon of physiological and pathophysiological importance termed aerobic glycolysis. Previous studies have proposed glutamate and K(+) as the neuronal signals that trigger aerobic glycolysis in astrocytes. Here we used a panel of genetically encoded FRET sensors in vitro and in vivo to investigate the participation of NH4(+), a by-product of catabolism that is also released by active neurons. Astrocytes in mixed cortical cultures responded to physiological levels of NH4(+) with an acute rise in cytosolic lactate followed by lactate release into the extracellular space, as detected by a lactate-sniffer. An acute increase in astrocytic lactate was also observed in acute hippocampal slices exposed to NH4(+) and in the somatosensory cortex of anesthetized mice in response to i.v. NH4(+). Unexpectedly, NH4(+) had no effect on astrocytic glucose consumption. Parallel measurements showed simultaneous cytosolic pyruvate accumulation and NADH depletion, suggesting the involvement of mitochondria. An inhibitor-stop technique confirmed a strong inhibition of mitochondrial pyruvate uptake that can be explained by mitochondrial matrix acidification. These results show that physiological NH4(+) diverts the flux of pyruvate from mitochondria to lactate production and release. Considering that NH4(+) is produced stoichiometrically with glutamate during excitatory neurotransmission, we propose that NH4(+) behaves as an intercellular signal and that pyruvate shunting contributes to aerobic lactate production by astrocytes.
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