Sodium fluoride exposure induced cognitive impairment via disorders synaptic protein expression and neuronal...

As an environmental pollutant, fluoride is widespread in the natural environment in different forms, and drinking water is the primary way of exposure in human and animals. Structural damage to the central nervous system may occur in human and animals after fluoride exposure, which can lead to cognitive dysfunction. However, the mechanism of cognitive impairment caused by fluoride remains unclear. In this research, a fluoride-exposed model of mice and HT-22 cells was established to explore the neurotoxic mechanisms of fluoride. In vitro, CCK-8 results showed that HT-22 cells decreased with the increase in fluoride concentrations, and the morphology appeared abnormal. Similarly, laser confocal microscopy revealed that the number of axons and dendrites decreased with the increase in fluoride concentrations. Western blot results showed that the expression level of synaptic and cytoskeleton-associated proteins decreased in fluoride groups. In vivo, the mice exhibited losses in body and brain weights in the fluoride groups compared with the control group. The step-down test demonstrated that the cognitive ability of mice in the fluoride groups significantly decreased compared with that in the control group. Western blot results showed that the expression of synaptic and cytoskeleton-associated proteins decreased in the low-fluoride group compared with the control group, and qRT-PCR results showed that PSD95 expression decreased significantly compared with the control group. These results indicated that cognitive impairment induced by fluoride is involved in the morphological damage of synapse and the abnormal expression of synaptic proteins.