Background: The zebrafish has become an established model organism in aging research giving insight into general aging processes in vertebrates. Oxidative stress in aging may damage proteins and lipids in brain cells. Enhanced levels of oxidized macromolecules exert neurotoxic effects that could lead to disturbances in neuronal functioning and cognitive skills. Objective: This study aims to investigate a possible relation between oxidative stress and learning deficits during aging in zebrafish. Methods: We tested zebrafish of different ages in a color discrimination paradigm for associative learning and in a hole board task for spatial learning abilities. Afterwards, we determined the levels of oxidized lipids and proteins as well as the amount of lipofuscin in the learning-relevant brain regions of animals of the same age. Results: While young zebrafish at the age of 1 year successfully completed both learning tasks, cognitive abilities were significantly impaired in older animals. Learning deficits occurred at the age of 2 years, where we also detected significantly increased levels of lipofuscin and oxidized proteins in the zebrafish medial and lateral pallial areas of the dorsal telencephalon. Conclusion: These data suggest that enhanced oxidative stress may contribute to behavioral and cognitive impairments in the aging zebrafish.

The results are very coincident with reports on mammals, demonstrating that the ECS is functional highly conserved during vertebrate evolution. We further conclude that the zebrafish provides a promising model organism for ongoing research on the ECS.