Determining the role of lactate metabolism on age‐dependent memory decline and neurodegeneration in <i>Drosophila melanogaster</i>
Bibliographic record
Abstract
Abstract Background Although lactate has traditionally been considered a waste product, recent discoveries show lactate plays many beneficial roles in the brain. Astrocyte generated lactate can function as a fuel for neurons to enable long‐term memory. However, elevated lactate has been detected within the brain and cerebrospinal fluid of Alzheimer’s disease patients; a finding associated with hastened memory impairment. Whether perturbed lactate levels contribute to age‐related memory impairment is unknown. This study uses the fruit fly Drosophila melanogaster to elucidate the role of lactate metabolism in cognition during aging. Method The enzyme lactate dehydrogenase (dLdh), which facilitates the interconversion between lactate and pyruvate, was genetically manipulated in glia and neurons of Drosophila melanogaster. Transgenic flies were tested for changes in lifespan, memory, climbing ability, neurodegeneration as well as dLdh and lactate levels in the brain. Tests in transgenic flies were performed at ages ranging from young (7 days) to old (28 days). Memory was assessed using the courtship conditioning paradigm, of which only male flies can be tested. Results Lactate and dLdh protein levels were correspondingly elevated or lowered in transgenic flies with increased or decreased dLdh expression respectively. Transgenic flies with either increased or decreased dLdh expression exhibited reduction in lifespan and neurodegeneration at old age. These detrimental effects were present whether dLdh expression was altered in either neurons or glia, yet only neuronal dLdh upregulation caused deficits in climbing ability. Young transgenic flies with altered dLdh expression in either neurons or glia all exhibited memory similar to control. Interestingly, only flies with increased glial‐derived dLdh expression had an impact; memory was impaired at middle age then recovered at old age. Conclusion Prolonged perturbation of lactate metabolism results in neurodegeneration and increased rate of health decline in flies. The impact of altered lactate levels on memory appears to be cell type specific and dynamic. Excess glial‐derived lactate only appears detrimental to memory during middle age. However, excess or diminished production of lactate, within neurons or glia, hastens aging and neurodegeneration. Future studies of age‐related diseases, such as Alzheimer’s, should focus on lactate metabolism and metabolic interplay between neurons and glia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".