Autophagy May Be Involved in Fluoride-Induced Learning Impairment in Rats.

Fluoride can induce neurotoxicity, but the mechanism is not clear. In this study, we explored the role of autophagy in F--induced neurotoxicity of Wistar rats. Eighty Wistar rats were randomly divided into four groups: the control group (distilled water containing less than 0.1 mg/L F-) and three NaF-treated groups (F- was respectively administered at 25, 50, and 100 mg/L orally via drinking water). The water maze experiment showed that NaF exposure impaired the learning capabilities of the rats. When compared with the control group, the mean escape latency of the rats in the 100 mg/L F- group was much longer (P < 0.05). Immunohistochemical analysis showed that NaF exposure induced autophagy, as shown by the significant increase of Beclin-1 expression in the hippocampal CA1 region and DG region. Transmission electron microscopy was used to observe the ultrastructural changes of hippocampal neurons. With the increase of F- concentration, the ultrastructural abnormalities of hippocampal neurons increased. These results indicate that fluoride can impair the learning ability of rats, which may be related to the induction of autophagy in rat hippocampal neurons.