Effects of low concentration of fluoride exposure during fetal on behavior and neurotransmitters in adult mice

Fluoride (F) naturally occurs in water in China and India, and in excess, can cause skeletal fluorosis and mottled teeth. Chronic exposure to F during gestation can affect the development of the brain, reducing intelligence quotient and inducing autism spectrum disorder-like behavior. In the present study, it was aimed to clarify the effects of chronic exposure to low concentrations of F <i>in utero</i> on brain function. The behavior was assessed, the levels of brain neurotransmitters were measured in mice and their relationships were analyzed. ICR mice consumed water containing sodium fluoride (F concentrations: 0, 15, or 30 ppm) from 3 weeks of age until the weaning of their pups (F1). The pups then consumed water containing the same concentration of F as their parents from weaning. At 8-weeks old, the F1 mice underwent behavioral testing using the Y-maze, elevated plus maze, Barnes maze (BM) and open-field test (OFT). At 10 weeks of age, they were euthanized, their brains were collected, and the levels of neurotransmitters were measured. Grooming events in the OFT were more frequent in F-exposed groups than in the control group, indicating that F exposure causes anxiety-like behavior. In the BM, the time taken to reach the escape box and the number of errors were higher during the training and test, suggesting spatial memory impairment. Cerebellar glutamate (Glu) concentrations were significantly lower in the F-exposed groups than in the control group. Low Glu concentration was associated with greater grooming frequency in the OFT, lower mean speed and more errors in the BM, and a delay in reaching the escape box. In the F-exposed groups, the midbrain noradrenaline concentrations were significantly lower and the number of errors in the BM was larger than in controls. Thus, F-exposed mice showed poorer spatial memory and differences in the levels of neurotransmitter, suggesting that F is an environmental contributor to disease.