Bagwe_2025_Fish.Physiol.Biochem_51_160

Zebrafish models have been used to research Alzheimer's disease and other neurodegenerative disorders because of their similarities to the human genetic composition and behavior. Researchers have detected iron accumulation in the post-mortem brain sections of neurodegenerative disorder patients. Therefore, the development an animal model to simulate these clinical pathological findings is important. Iron is an important metal for maintaining homeostasis in the brain, depletion and accumulation of iron hamper neuronal development. Given the importance of iron overload in cognition impairment, this research aimed to develop an iron-induced zebrafish model of cognitive impairment. Zebrafish were subjected to ferrous sulfate (1.5 mg/L, 3 mg/L, and 6 mg/L) for 28 days. The behavioral parameters (Y-maze, novel tank test), oxidative stress parameters (MDA, GSH, and catalase), acetylcholinesterase (AChE) levels, iron levels, and interleukin-1beta (IL-1beta) levels in brain homogenate were assessed. The behavioral and locomotor responses, specifically in the zebrafish treated with iron for 28 days, suggest an increase in the loss of spatial memory and anxiety. Reactive oxygen species in the brain significantly increased (p<0.001) with the increase in concentrations of iron. Brain tissue iron content and IL-1beta significantly increased (p<0.001) in the brain homogenate of the zebrafish. This model will aid in the screening of therapeutic compounds to accelerate drug discovery in the field of neurodegenerative diseases.