ArticleProceedings of the National Academy of Sciences of the United States of America2021
Lactate transporters in the rat barrel cortex sustain whisker-dependent BOLD fMRI signal and behavioral performance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 42 citations in OpenAlex.
- BOLD repetition enhancement in the orbitofrontal cortex during complex visuospatial processing in migraine without aura: a shift in periaqueductal gray - cortical coupling?The journal of headache and pain · 2026Article
- Neuronal MCT2 promotes angiogenesis via lactate in the developing mouse neocortex.Cell death and differentiation · 2026Article
- Lactate: elucidating its indispensable role in human health.Molecular cancer · 2026Review
- Lactate and lactylation in sepsis: regulation of immune-metabolic crosstalk and organ injury.Frontiers in immunology · 2026Review
- The neuron-astrocyte metabolic unit as a cornerstone of brain energy metabolism in health and disease.Nature metabolism · 2025Review
- Hypothalamic Astrocytes Exhibit Glycolytic Features Making Them Prone for Glucose Sensing.Glia · 2025Article
- A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular L-lactate dynamics.Nature communications · 2025Article
- Positive impact of sodium L-lactate supplementation on blood acid-base status in preterm newborns.Pediatric research · 2025Article
- Article
- Neural Metabolic Networks: Key Elements of Healthy Brain Function.Journal of neurochemistry · 2025Review
- Construction of a diagnostic prediction model for ischemic stroke using lactylation-related genes.Frontiers in molecular neuroscience · 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
- Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture.Nature communications · 2024Article
- Neuroprotective effects of lactate and ketone bodies in acute brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- Neurovascular coupling is optimized to compensate for the increase in proton production from nonoxidative glycolysis and glycogenolysis during brain activation and maintain homeostasis of pH, pCOJournal of neurochemistry · 2024Article
- Article
- Astrocytes: Lessons Learned from the Cuprizone Model.International journal of molecular sciences · 2023Review
- Astrocyte-neuron lactate shuttle plays a pivotal role in sensory-based neuroprotection in a rat model of permanent middle cerebral artery occlusion.Scientific reports · 2023Article
- Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance.Journal of neurochemistry · 2023Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lactate is an efficient neuronal energy source, even in presence of glucose. However, the importance of lactate shuttling between astrocytes and neurons for brain activation and function remains to be established. For this purpose, metabolic and hemodynamic responses to sensory stimulation have been measured by functional magnetic resonance spectroscopy and blood oxygen level-dependent (BOLD) fMRI after down-regulation of either neuronal MCT2 or astroglial MCT4 in the rat barrel cortex. Results show that the lactate rise in the barrel cortex upon whisker stimulation is abolished when either transporter is down-regulated. Under the same paradigm, the BOLD response is prevented in all MCT2 down-regulated rats, while about half of the MCT4 down-regulated rats exhibited a loss of the BOLD response. Interestingly, MCT4 down-regulated animals showing no BOLD response were rescued by peripheral lactate infusion, while this treatment had no effect on MCT2 down-regulated rats. When animals were tested in a novel object recognition task, MCT2 down-regulated animals were impaired in the textured but not in the visual version of the task. For MCT4 down-regulated animals, while all animal succeeded in the visual task, half of them exhibited a deficit in the textured task, a similar segregation into two groups as observed for BOLD experiments. Our data demonstrate that lactate shuttling between astrocytes and neurons is essential to give rise to both neurometabolic and neurovascular couplings, which form the basis for the detection of brain activation by functional brain imaging techniques. Moreover, our results establish that this metabolic cooperation is required to sustain behavioral performance based on cortical activation.
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