ArticleNature communications2024
A lactate-dependent shift of glycolysis mediates synaptic and cognitive processes in male mice.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effects of lactate-based therapies on intracranial pressure and brain metabolism of patients with acute brain injury: a systematic review.Critical care (London, England) · 2026Pooled it
- Brain mitochondria as key drivers of cognition and behaviour.Nature reviews. Neuroscience · 2026Review
- Review
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
- Lactate treatment improves brain biochemistry and cognitive function in transgenic Alzheimer's and wild-type mice.Scientific reports · 2026Article
- Astrocytic GPR55 receptors promote glycolysis.Journal of cannabis research · 2026Article
- Acceleration of Lactate Uptake and Utilization Contributes to Neuroprotective Action of FGF21 Involved in Naturally Aging Mice.Aging cell · 2026Article
- APOE-ε4 genotype and western diet synergistically aggravate synaptic dysfunction in Alzheimer's disease via D-serine disruption.Alzheimer's research & therapy · 2026Article
- Signaling roles for astrocytic lipid metabolism in brain function.EMBO reports · 2026Review
- Astrocyte CBJournal of neuroinflammation · 2026Article
- ZBTB7A-mediated regulation of astrocytic glycolysis in neurodegenerative diseases: insights from literature review and bioinformatics prediction.Frontiers in aging neuroscience · 2026Review
- NAD⁺ Reduction in Glutamatergic Neurons Induces Lipid Catabolism and Neuroinflammation in the Brain via SARM1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Cannabinoid Ligand-Mediated Glycogen Depletion in Astrocytes Is Associated With Increased Intracellular Calcium, Energy Metabolism, and Membrane Dynamics.Journal of neurochemistry · 2025Article
- The neuron-astrocyte metabolic unit as a cornerstone of brain energy metabolism in health and disease.Nature metabolism · 2025Review
- Break free from cognitive impairment: The magic of exercise-induced molecules.Brain, behavior, & immunity - health · 2025Review
- D-Serine's Journey Between Stars and Synapses.Neurochemical research · 2025Review
- GPR55 senses lactate to sustain motility in prostate cancer cells.Molecular and cellular biochemistry · 2025Article
- Calcium dynamics in habenular astrocytes regulate active coping within behavioral transitions.Communications biology · 2025Article
- The Endocannabinoid System in Retinal Müller Glia: Lessons From Astrocyte Research.Neurochemical research · 2025Review
Corrections and comments
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Authors and funding
26 authors.
Funding
Abstract
Astrocytes control brain activity via both metabolic processes and gliotransmission, but the physiological links between these functions are scantly known. Here we show that endogenous activation of astrocyte type-1 cannabinoid (CB1) receptors determines a shift of glycolysis towards the lactate-dependent production of D-serine, thereby gating synaptic and cognitive functions in male mice. Mutant mice lacking the CB1 receptor gene in astrocytes (GFAP-CB1-KO) are impaired in novel object recognition (NOR) memory. This phenotype is rescued by the gliotransmitter D-serine, by its precursor L-serine, and also by lactate and 3,5-DHBA, an agonist of the lactate receptor HCAR1. Such lactate-dependent effect is abolished when the astrocyte-specific phosphorylated-pathway (PP), which diverts glycolysis towards L-serine synthesis, is blocked. Consistently, lactate and 3,5-DHBA promoted the co-agonist binding site occupancy of CA1 post-synaptic NMDA receptors in hippocampal slices in a PP-dependent manner. Thus, a tight cross-talk between astrocytic energy metabolism and gliotransmission determines synaptic and cognitive processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.