The Impact of Aging and Antioxidants on the Recovery from Spreading Depolarization in Locusts

Academic Background

Spreading Depolarization (SD) is a phenomenon that temporarily shuts down neural processing in both mammals and insects. In humans, SD is associated with various pathological states, such as migraine aura and neuronal death following traumatic brain injury. However, in insects, SD is considered a mechanism for temporarily conserving energy during environmental challenges. Although the manifestations of SD differ between mammals and insects, the underlying mechanisms may be similar. Age is a critical factor influencing the consequences of SD, particularly in humans, where elderly patients exhibit poorer recovery from SD. However, there is limited research on how age affects SD recovery in insect models and the role of oxidative stress in this process.

This study aims to explore the impact of aging on SD recovery in a locust model and investigate the role of oxidative stress in this process. By using locusts as a model, the researchers hope to uncover common mechanisms of SD in insects and mammals and provide new insights into the effects of SD in the aging nervous system.

Source of the Paper

This paper was authored by R. Meldrum Robertson and Yuyang Wang from the Department of Biology at Queen’s University, Canada. It was first published on December 12, 2024, in the Journal of Neurophysiology, with the DOI 10.1152/jn.00487.2024.

Research Process

1. Experimental Subjects and Grouping

The study used locusts (Locusta migratoria) as experimental subjects. The locusts were sourced from a long-established colony maintained at Queen’s University. The experiments were divided into two groups: young locusts (3-4 weeks old) and old locusts (>7 weeks old). Each group was randomly assigned to different treatment groups, including a control group, an antioxidant treatment group (N-acetylcysteine amide, NACA), and an oxidative stress inducer group (Rotenone).

2. Water Submersion Experiment

First, the researchers induced anoxic coma by submerging the locusts in water and observed their recovery. The experiment recorded the time taken for the locusts to enter a coma (time to coma), the time to resume breathing (time to ventilate), and the time to fully recover and stand (time to stand). The results showed that old locusts took significantly longer to recover breathing and standing compared to young locusts, indicating that age affects the recovery ability of locusts from anoxia.

3. Electrophysiological Recording

Next, the researchers conducted electrophysiological recordings using semi-intact preparations of the locust thoracic ganglia. By recording the DC potential across the blood-brain barrier, the researchers monitored the occurrence and recovery of SD events. The Na+/K+-ATPase inhibitor ouabain was used to induce SD, and parameters such as the duration of SD events and recovery rates were recorded.

4. Oxidative Stress and Antioxidant Treatment

To investigate the effects of oxidative stress on SD, the researchers used Rotenone (a mitochondrial complex I inhibitor) to induce oxidative stress and NACA (an antioxidant) to mitigate oxidative stress. The results showed that Rotenone treatment had no significant effect on SD events, while NACA treatment significantly shortened the duration of SD events and accelerated recovery rates.

Key Findings

1. Impact of Age on SD Recovery: Old locusts took significantly longer to recover from anoxia compared to young locusts, indicating that age affects the tolerance and recovery ability of locusts to anoxia.

2. Electrophysiological Characteristics of SD Events: Ouabain-induced SD events lasted longer and had slower recovery rates in old locusts. This suggests that the ability of the nervous system in old locusts to restore ion gradients after SD events is diminished.

3. Role of Antioxidants: NACA treatment significantly shortened the duration of SD events and accelerated recovery rates, indicating that antioxidants can mitigate the negative effects of oxidative stress on SD recovery.

4. Role of Oxidative Stress Inducers: Rotenone treatment had no significant effect on SD events, possibly because the concentration used was insufficient to induce significant oxidative stress.

Conclusion

This study reveals the significant impact of aging on SD recovery in locusts and demonstrates the critical role of oxidative stress in this process. By using the antioxidant NACA, the researchers successfully accelerated the recovery rates of SD events, suggesting that antioxidants could serve as a potential therapeutic approach to improve the recovery ability of the aging nervous system following SD events.

Research Highlights

1. Relationship Between Age and SD Recovery: This study is the first to systematically investigate the impact of aging on SD recovery in an insect model, providing new insights into the role of SD in the aging nervous system.

2. Role of Antioxidants: The study found that the antioxidant NACA significantly improved the recovery rates of SD events, offering new ideas for developing therapeutic strategies targeting SD.

3. Application of Electrophysiological Recording Techniques: By recording the DC potential across the blood-brain barrier, the researchers successfully monitored the occurrence and recovery of SD events, providing a powerful tool for studying the mechanisms of SD.

Research Value

This study not only deepens our understanding of the common mechanisms of SD in insects and mammals but also provides new ideas for developing therapeutic strategies targeting SD. In particular, the role of antioxidants in improving SD recovery rates offers important experimental evidence for future research. Additionally, this study provides a new model and methodology for studying the functional decline of the aging nervous system.