Abstract: Objective To explore the effects of fluoride and arsenic on ultrastructure of hippocampus and cerebral cortical neurons and cynapses in rats.Methods The Sprague-Dawley rats at the beginning of weaning were randomly divided into four groups.The rats in fluoride and arsenic group were exposed to 120 mg/L sodium fluoride (NaF)and 70 mg/L sodium arsenite (NaAsO₂),respectively,and the fluoride and arsenic co-exposure rats were exposed to 120 mg/L NaF and 70 mg/L NaAsO₂ combined solution as drinking water for ninety days.The control rats drank distilled water for ninety days.Electron microscope samples were made in order to observe ultrastructural changes of neurons in hippocampus and cerebral cortex by transmission electron microscope(TEM).Results The levels of fluoride in hippocampus and cerebral cortex tissues in NaF-exposed and co-exposed rats were 1.14±0.35,1.06±0.27 and 1.19±0.42,1.03±0.21 μg/g,respectively,and all much higher than those in the control(0.24±0.18 and 0.25±0.07 μg/g)and NaAsO₂-exposed rats(0.48±0.10 and 0.41±0.03 μg/g)(all P<0.01).The levels of arsenic in hippocampus and cerebral cortex tissues in NaAsO₂-exposed and co-exposed rats were 3.92±0.63,3.80±0.76 and 3.73±0.99,3.43±0.63 μg/g,respectively,and all much higher than those in the control(0.16±0.03 and 0.14±0.02 μg/g)and NaF-exposed rats(0.16±0.02 and 0.16±0.03 μg/g)(all P<0.01).The ultrastructure in hippocampus and cortex neurons in the NaF-exposed,NaAsO₂-exposed and co-exposed rats all had pathological changes.There were obvious changes such as cell shrinkage,nuclear deformation,perinuclear mitochondrial swelling and cavitating.The pathological changes of cynapses were also observed for synaptic vesicles of presynaptic and postsynaptic membrane and the mitochondria ridge was incomplete,the synaptic cleft was expanded,and the mitochondria in postsynaptic membrane was swelled and cavitated.Conclusion Subchronic exposure to fluoride and arsenic may cause evident pathological changes in ultrastructure of hippocampus and cortex neurons and cynapses.