Exposure to malathion impairs learning and memory of zebrafish by disrupting cholinergic signal transmission, undermining synaptic plasticity, and aggravating neuronal apoptosis

The prevalence of organophosphorus pesticides, such as malathion, in water environments poses a severe threat to aquatic organisms. Although the brain is a potential target for malathion, little is known about its effect on cognitive functions in fish. In this study, we evaluated the effect of 4-week malathion exposure on the learning and memory of zebrafish using T-maze tasks. In addition to verifying the accumulation of malathion in the brain and its deleterious effects on blood-brain barrier integrity, the impacts of malathion on cholinergic signal transmission, synaptic plasticity, apoptosis, and oxidative stress were determined. Our results demonstrated that a 4-week malathion exposure resulted in typical learning and memory-deficit-like behaviors. Apart from inhibiting cholinergic signal transmission, synaptic plasticity was severely undermined by malathion (as evidenced by the disruption of BDNF/PI3K/AKT/CREB pathway, suppression of synaptophysins, and activation of microglia). Moreover, significantly higher levels of TUNEL fluorescence signals as well as apoptotic enzymes and genes probably induced by oxidative stress were detected in the brains of malathion-exposed zebrafish. Collectively, our results suggested that malathion at environmentally realistic levels can significantly undermine learning and memory of zebrafish by disrupting cholinergic signal transmission, impairing synaptic plasticity, and aggravating neuronal apoptosis via inducing oxidative stress.