{
"title": "Astrocyte vs neuron metabolic preference: evidence for and against ANLS across methods",
"papers": [
{
"doi": "10.1073/pnas.91.22.10625",
"assay": "Primary mouse astrocyte cultures; 2-DG uptake, lactate output",
"value": "Glutamate stimulates glycolysis in astrocytes (glucose utilization and lactate production)",
"metric": "Astrocytic glucose utilization and lactate release in response to glutamate (Na+-coupled uptake)",
"effect_size": "Stoichiometric coupling: ~1 glucose used and 2 lactate produced per glutamate taken up",
"intervention": "Glutamate (Na+-dependent uptake)",
"effect_direction": "Astrocytic glycolysis and lactate release increase",
"first_author_year": "Pellerin & Magistretti 1994",
"baseline_or_control": "Unstimulated astrocytes",
"value_source_sentence": "Here we report that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis--i.e., glucose utilization and lactate production--in astrocytes."
},
{
"doi": "10.1523/jneurosci.0026-12.2012",
"assay": "Rat hippocampal slices; O2 electrode + NADH two-photon imaging; ATP energy budget",
"value": "Rapid activity-driven decrease of extracellular O₂ and intracellular NADH even with LDH blocked or at 20% superfused O₂",
"metric": "Activity-evoked change in extracellular O₂ and intracellular NADH in rat hippocampal slices with LDH blocked",
"effect_size": "Presynaptic APs ≈ 11%, Ca2+ entry ≈ 17%, postsynaptic currents ≈ 50% of activity-driven ATP; NADH decrease persists with LDH blocked",
"intervention": "Schaffer collateral stimulation",
"effect_direction": "Activity evokes oxidative response in neurons",
"first_author_year": "Hall et al. 2012",
"baseline_or_control": "Resting",
"value_source_sentence": "Neural activity has been suggested to initially trigger ATP production by glycolysis, rather than oxidative phosphorylation, for three reasons: glycolytic enzymes are associated with ion pumps; neurons may increase their energy supply by activating glycolysis in astrocytes to generate lactate; and activity increases glucose uptake more than O₂ uptake."
},
{
"doi": "10.1038/ncomms7807",
"assay": "Two-photon 2DG-IR imaging, awake mouse somatosensory cortex",
"value": "Glucose taken up preferentially by neurons (not astrocytes) in awake behaving mice",
"metric": "Cellular distribution of in vivo 2-DG analogue (2DG-IR) uptake during awake sensory stimulation, neurons vs astrocytes",
"effect_size": "Neuronal 2DG-IR signal exceeds astrocytic signal during activity; hexokinase-I enriched in neurons",
"intervention": "Whisker stimulation",
"effect_direction": "Neurons take up glucose preferentially over astrocytes",
"first_author_year": "Lundgaard et al. 2015",
"baseline_or_control": "Unstimulated",
"value_source_sentence": "Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice."
},
{
"doi": "10.1073/pnas.1322912111",
"assay": "Rat cortical synaptosomes; 19F NMR of 2-FDG; pyruvate carboxylase activity",
"value": "Activity-induced lactate release followed by rapid glucose phosphorylation in presynaptic nerve terminals",
"metric": "Glucose phosphorylation by isolated cortical nerve terminals (synaptosomes) after activity-induced lactate release",
"effect_size": "Activity-dependent glucose uptake in isolated nerve terminals",
"intervention": "K+ depolarization",
"effect_direction": "Neuronal (synaptosomal) glucose uptake and pyruvate carboxylase activity rise",
"first_author_year": "Bak et al. 2014",
"baseline_or_control": "Resting",
"value_source_sentence": "L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate."
},
{
"doi": "10.1016/j.cmet.2015.10.010",
"assay": "Laconic FRET sensor + two-photon imaging, mouse cortex in vivo",
"value": "Astrocyte-to-neuron lactate gradient (astrocyte lactate higher than neuron)",
"metric": "Steady-state lactate content of cortical astrocytes vs neurons measured in vivo with Laconic FRET sensor + two-photon microscopy",
"effect_size": "Astrocyte–neuron lactate gradient detectable in vivo",
"intervention": "Intravenous lactate injection; baseline compartmental measurement",
"effect_direction": "Lactate concentration higher in astrocytes than neurons; gradient consistent with astrocyte-to-neuron flux",
"first_author_year": "Machler et al. 2016",
"baseline_or_control": "Astrocyte vs neuron steady-state",
"value_source_sentence": "Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons."
}
],
"description": "Quantitative and imaging comparisons of glucose/lactate metabolism between astrocytes and neurons yield contradictory conclusions depending on method and preparation."
}