Recovery from Spreading Depolarization is slowed by aging and accelerated by antioxidant treatment in locusts
Bibliographic record
Abstract
Abstract Spreading depolarization (SD) temporarily shuts down neural processing in nervous systems with effective blood brain barriers. In mammals this is usually pathological in response to energetic stress. In insects a very similar process is induced by abiotic environmental stressors and can be beneficial by conserving energy. Age is a critical factor for predicting the consequences of SD in humans. We investigated the effect of aging on SD in an insect model of SD and explored the contribution of oxidative stress. Aging slowed the recovery of intact locusts from asphyxia by water submersion. In semi-intact preparations we monitored SD by recording the DC potential across the blood brain barrier in response to bath application of the Na + /K + -ATPase inhibitor, ouabain. Treatment with ouabain induced changes to the DC potential that could be separated into two distinct components: a slow, permanent negative shift, similar to the negative ultraslow potential recorded in mammals and human patients, as well as rapid, reversible negative DC shifts (SD events). Aging had no effect on the slow shift but increased the duration of SD events from ∼0.6 minutes in young locusts to ∼0.9 minutes in old ones. This was accompanied by a decrease in the rate of recovery of DC potential at the end of the SD event, from ∼1.5 mV/s (young) to ∼0.6 mV/s (old). An attempt to generate oxidative stress using rotenone was unsuccessful, but pretreatment with the antioxidant, N-acetylcysteine amide, had opposite effects to those of aging, reducing duration (control ∼1.1 minutes, NACA ∼0.7 minutes) and increasing rate of recovery (control ∼0.5 mV/s, NACA ∼1.0 mV/s) suggesting that it prevented oxidative damage occurring during the ouabain treatment. The antioxidant also reduced the rate of the slow negative shift. We propose that the aging locust nervous system is more vulnerable to stress due to a prior accumulation of oxidative damage. Our findings also strengthen the notion that insects provide useful models for the investigation of cellular and molecular mechanisms underlying SD in mammals. Significance Statement Anoxia and similar energetic crises trigger a shutdown of central neural processing in a process of spreading depolarization (SD) which is generally pathological in mammals and protective in insects. We show that some variability in the consequences of SD in an insect model can be attributed to age, such that older animals are slower to recover. Moreover, preventing oxidative stress with an antioxidant speeds recovery. These findings demonstrate a role for oxidative stress in contributing to the vulnerability of the aging insect CNS in energetic emergencies. Abstract Figure Graphical Abstract of Robertson and Wang - Locust Spreading Depolarization
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".