Dual roles of reactive oxygen species in ascidian brain regeneration and degeneration

Abstract

Reactive oxygen species (ROS) are metabolically generated by neural cells and are essential for maintaining cellular homeostasis. Due to the high metabolic activity and oxygen consumption of the nervous system, large amounts of ROS are produced. Although ROS are traditionally associated with oxidative stress and degeneration, recent studies suggest that they may also play a beneficial role in neural repair. To explore the role of ROS in central nervous system (CNS) regeneration, we employed the adult ascidian Styela plicata, which can regenerate its entire brain within 10 days, as a model. We aimed to elucidate the functions of ROS and the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the formation of synapses and/or cell proliferation in the CNS of the ascidian S. plicata following the systemic injection of the neurotoxin 3-acetylpyridine (3-AP). The data revealed two distinct periods of high ROS production: at 0.5 and 5 days. SOD and CAT activity increased only at 5 days. Lipid peroxidation was highest at 0.5 days and gradually decreased during the 10 day post-injection monitoring period. The proliferation marker Ki-67 and the synapse marker synaptophysin were elevated at 3 and 5 days, respectively. These findings suggest a dual role for ROS: an early phase linked to neurodegeneration and a later phase associated with regeneration. This highlights the complex role of redox signaling in CNS regeneration.