Version history

{
  "kind": "infographic",
  "prompt": "L-lactate rescue of glycogenolysis/MCT blockade across behavior and plasticity assays",
  "provider": "other",
  "raw_fields": {
    "title": "L-lactate rescue of glycogenolysis/MCT blockade across behavior and plasticity assays",
    "papers": [
      {
        "doi": "10.1016/j.cell.2011.02.018",
        "assay": "Inhibitory avoidance (24 h retention) in rat hippocampus; microdialysis-measured lactate",
        "value": "Amnesia induced by DAB and by MCT1/2/4 antisense; L-lactate (but not equicaloric glucose) rescues amnesia except for MCT2 (neuronal) knockdown",
        "metric": "Effect of DAB / MCT1/2/4 antisense knockdown on 24 h inhibitory-avoidance retention, and L-lactate vs glucose rescue",
        "effect_size": "Training-induced ECF lactate rise ~170–190% above baseline; DAB blocks rise and abolishes 24 h retention (n=6–12 rats/group)",
        "intervention": "DAB (glycogenolysis block); antisense ODNs against MCT1/4 (astrocyte), MCT2 (neuron)",
        "effect_direction": "Amnesia induced; rescued by L-lactate (not glucose) except MCT2 block",
        "first_author_year": "Suzuki et al. 2011",
        "baseline_or_control": "Vehicle / scrambled ODN",
        "value_source_sentence": "L-lactate, but not equicaloric concentrations of glucose, rescues these MCT1- MCT2- or MCT4-knock-down-dependent amnesia, indicating that glucose and lactate are not functionally interchangeable."
      },
      {
        "doi": "10.1371/journal.pone.0028427",
        "assay": "Spatial working memory (8-arm radial maze), rat hippocampus",
        "value": "DAB impairs spatial working memory; exogenous L-lactate rescues",
        "metric": "Effect of intrahippocampal glycogenolysis inhibitor (DAB) on 8-arm radial maze working memory, with L-lactate rescue",
        "effect_size": "DAB reduces correct arm entries; rescue with 100 mM L-lactate (n=12–15/group)",
        "intervention": "DAB intrahippocampal infusion; L-lactate co-infusion rescue",
        "effect_direction": "DAB impairs working memory; lactate rescues",
        "first_author_year": "Newman et al. 2011",
        "baseline_or_control": "Saline / vehicle",
        "value_source_sentence": "Discussion The data reported here support the view that, in the hippocampus, glycogenolysis in astrocytes, and subsequent delivery of lactate to neurons, is important for spatial working memory."
      },
      {
        "doi": "10.1093/cercor/bhz226",
        "assay": "Novel object recognition + ex vivo LTP + 3D-EM spine morphology, mouse hippocampal CA1",
        "value": "During learning, astrocytic glycogen is broken down to provide lactate; this lactate supply is necessary for spine remodeling and memory formation",
        "metric": "Effect of learning on astrocytic glycogen and lactate supply to neurons, and requirement for spine remodeling and memory",
        "effect_size": "Training increases glycogen granule size/density; DAB abolishes and blocks spine enlargement",
        "intervention": "DAB; L-lactate rescue",
        "effect_direction": "DAB impairs learning, LTP, and spine remodeling; lactate rescues",
        "first_author_year": "Vezzoli et al. 2020",
        "baseline_or_control": "Saline",
        "value_source_sentence": "A source of lactate in the brain, in addition to glucose, is glycogen ( Dringen and Hamprecht 1992 ), the storage form of glucose, which is exclusively localized in astrocytes ( Nelson et al."
      },
      {
        "doi": "10.1038/mp.2015.157",
        "assay": "Cocaine conditioned place preference, rat hippocampus",
        "value": "MCT1 or MCT4 down-regulation impairs long-term cocaine-CPP memory; L-lactate rescues",
        "metric": "Effect of bilateral hippocampal MCT1 or MCT4 knockdown on cocaine conditioned place preference, with L-lactate rescue",
        "effect_size": "Impaired long-term retention of cocaine CPP (n≈8/group)",
        "intervention": "Bilateral intrahippocampal antisense ODN against MCT1/MCT4; L-lactate rescue",
        "effect_direction": "Reduction of cocaine CPP; rescued by L-lactate",
        "first_author_year": "Boury-Jamot et al. 2016",
        "baseline_or_control": "Scrambled ODN",
        "value_source_sentence": "Therefore, we investigated whether disrupting the glycogen-derived L-Lactate release from astrocytes by administering an inhibitor of glycogen phosphorylase (1,4-dideoxy-1,4-imino- D -arabinitol (DAB)) into the BLA of rats was sufficient to impair the acquisition and/or the maintenance of a cocaine-induced conditioned place preference (CPP)."
      }
    ],
    "description": "Across multiple studies, pharmacological block of astrocytic glycogenolysis (DAB), MCT1/4 (astrocytic), or MCT2 (neuronal) impairs behavior and/or LTP. Exogenous L-lactate — but not equicaloric glucose — rescues outcomes in all but the neuronal MCT2 block (where lactate cannot re-enter the neuron)."
  },
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  "source_url": "https://github.com/AllenNeuralDynamics/ComputationalReviewAstrocytes/blob/1a55da0634a3bc04e5688792ed12141ce271d28e/evidence/section_06_evidence_package.json",
  "target_ref": "wiki_page:computationalreviewastrocytes-06",
  "review_repo": "ComputationalReviewAstrocytes",
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  "source_refs": [
    "paper:paper-16e6ed98049d",
    "paper:paper-1829615f8d75",
    "paper:paper-b7318ec88980",
    "paper:paper-baef06af1040"
  ],
  "section_title": "Metabolic Coupling and the Energy Substrate of Computation",
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      "Local review repositories are read-only inputs.",
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  "commit_sha": "1a55da0634a3bc04e5688792ed12141ce271d28e",
  "created_by": "persona-jerome-lecoq-gbo-neuroscience",
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}