Oligodendrogliopathy in Multiple Sclerosis: Relation to Low Glycolytic Metabolic Rate of Oligodendrocytes (I10.004)
Bibliographic record
Abstract
Objective: To determine the relationship between the bio-energetic properties of oligodendocytes (OLs) and their response to metabolic stresses that mimic the multiple sclerosis (MS) lesion micro-environment. Background: The production of myelin by OLs is a highly energetic process, requiring mitochondrial oxidative phosphorylation (OXPHOS) for ATP production and glycolysis/lactate to provide the carbon backbones necessary for lipid biosynthesis. Oligodendrogliopathy, which features the dying back of oligodendrocyte terminal processes, is a distinct type of injury response observed in MS lesions. This dying back process in MS has been linked to metabolic stress, which in MS lesions reflect disturbed micro-circulation with associated ischemia and/or production of toxic metabolites that disturb mitochondrial energy metabolism (Lassmann 2003). Methods: We used OLs isolated from adult human brain specimens to examine their injury responses (survival, process extension) to reduced trophic factor, low glucose, and hypoxia conditions as a model of oligodendrogliopathy observed in MS lesions. We further examined the underlying bio-energetic properties of OLs using a Seahorse XF96 extracellular flux analyzer under the basal, metabolic stress and recovery conditions. Results: Human OLs grown under the above stress conditions for 48 hours showed only a marginal increase in [percnt] of TUNEL+ cells but a significant decrease in process area per cell. Basal aerobic glycolysis under optimal conditions provides the majority of ATP production in OLs. Under stress conditions, this ATP production is significantly decreased. Removal of stress conditions for 48 hours allowed for recovery of ATP production that occurred under the metabolic stress conditions. Conclusions: Oligodendrocytes under metabolic stress conditions show significant reduction in glycolytic ATP production that is required for myelin maintenance. Here we show that the restoration of optimal metabolic conditions can restore energy production in human OLs. It remains to be determined when such intervention will result in long-term cell survival.
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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 | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".