Cerebral erythropoietin increases the hippocampal mitochondrial respiration during the postnatal development
Bibliographic record
Abstract
Mitochondrial respiration is the metabolic process in which ATP is formed as a result of electron transfer and substrate oxidation. However, in addition to this classic role, mitochondrial respiration, and the concomitant production of ROS, are also required to maintain ionic cell membrane gradients, develop synaptic pruning (axonal and dendritic growth), provide effective neurotransmission, modulate signaling pathways and regulate neurogenesis and differentiation. While all these processes occur during brain development, little is known about the regulation of mitochondrial respiration in the postnatal development of hippocampal tissue. In parallel, studies conducted over the past two decades demonstrated that cerebral erythropoietin (Epo) plays a crucial role in the development of the nervous system. Remarkably, Epo‐mediated neurodevelopment requires the activation of molecular mechanisms that are tightly associated with mitochondrial functions. Inline, recent published literature demonstrated that Epo modulates mitochondrial bioenergetics and control of oxidative stress in several tissues, including the brain. In this work, we evaluated the impact of Epo in the regulation of hippocampal mitochondrial respiration of mice during postnatal development. To do so, the hippocampus of wild type (WT) and transgenic mice constitutively overexpressing Epo in the brain only (Tg21) at postnatal ages 3 (P3), 7 (P7), 14 (P14), and 21 (P21) was collected. Mitochondrial oxygen consumption was measured by using our oxygraph‐2K system (O2k‐OROBOROS). Recording of the mitochondrial oxygen consumption was evaluated in 2 mg of tissue permeabilized with saponin, after the activation of complexes I (CI), I+II (C I+II), and IV (CIV). Our results showed that at P14 and P21, Epo in hippocampal tissue: 1) increases the mitochondrial respiratory activity; 2) increases the mitochondrial respiratory capacity; 3) maximizes the respiratory efficiency; and 4) augments the number mitochondria per tissue. Additional analysis, performed by using colorimetric assay kits, revealed that Epo at P14 increases the activity of superoxide dismutase (SOD). Altogether, our results suggest that Epo promotes an increased oxidative metabolism in the hippocampus at an age when this structure undergoes a full process of development and maturation. Support or Funding Information Jorge Soliz is supported by the “Fonds de recherche du Quebec‐Santé” (FRQ‐S; FQ121919)
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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".