Recovery from spreading depolarization is slowed by aging and accelerated by antioxidant treatment in locusts

Spreading depolarization (SD) temporarily shuts down neural processing in mammals and insects. Age is a critical factor for predicting the consequences of SD in humans. We investigated the effect of aging in an insect model of SD and explored the contribution of oxidative stress. Aging slowed the recovery of intact locusts from asphyxia. 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. Ouabain induced changes to the DC potential that could be separated into two distinct components: a slow, permanent negative shift, like the negative ultraslow potential recorded in mammals and human patients, and rapid, reversible negative DC shifts (SD events). Aging had no effect on the slow shift but increased the duration of SD events. This was accompanied by a decrease in the rate of recovery of DC potential at the end of the SD event. 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, and increasing rate of recovery, 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 strengthen the notion that insects provide useful models for the investigation of cellular and molecular mechanisms underlying SD in mammals.NEW & NOTEWORTHY Anoxia and similar energetic crises trigger a shutdown of central neural processing in a process of spreading depolarization (SD) that is generally pathological in mammals and protective in insects. We show that older animals are slower to recover from SD in an insect model. Moreover, preventing oxidative stress with an antioxidant speeds recovery. These findings demonstrate the role of oxidative stress in contributing to the vulnerability of the aging insect central nervous system (CNS) in energetic emergencies.