Inorganic fluoride and functions of brain

Although actively disputed and questioned, it has been proposed that chronic exposure to inorganic fluoride (F^-) is toxic for brain. The major question for this review was whether an excessive F^- intake is causally related to adverse neurological and cognitive health conditions in human beings and animals. The paper systematically and critically summarizes the findings of the studies showing positive associations between F^- intoxication and various intellectual defects, as well as of those which attempted to clarify the nature of F^- neurotoxicity. Many works provide support for a link between pre- and postnatal F^- exposure and structural and functional changes in the central nervous system responsible for neurological and cognitive disorders. The mechanisms suggested to underlie F^- neurotoxicity include the disturbances in synaptic transmission and synaptic plasticity, premature death of neurons, altered activities of components of intracellular signaling cascades, impaired protein synthesis, deficit of neurotrophic and transcriptional factors, oxidative stress, metabolic changes, inflammatory processes. However, the majority of works have been performed on laboratory rodents using such F^- doses which are never exist in the nature even in the regions of endemic fluorosis. Thus, this kind of treatment is hardly comparable with human exposure even taking into account the higher rate of F^- clearance in animals. Of special importance are the data collected on humans chronically consuming excessive F^- doses in the regions of endemic fluorosis or contacting with toxic F^- compounds at industrial sites, but those works are scarce and often criticized due to low quality. New, expertly performed studies with repeated exposure assessment in independent populations are needed to prove an ability of F^- to impair neurological and intellectual development of human beings and to understand the molecular mechanisms implicated in F^--induced neurotoxicity.