Decreased nicotinic receptors in PC12 cells and rat brains influenced by fluoride toxicity–a mechanism relating to a damage at the level in post-transcription of the receptor genes.

Shan KR, Qi XL, Long YG, Nordberg A, Guan ZZ. Toxicology. 2004 Aug 5;200(2-3):169-77.


In order to reveal mechanisms of the decreased nicotinic acetylcholine receptors (nAChRs) resulted from fluoride toxicity, we treated PC12 cells by different concentrations of fluoride (0.1-100 ppm) for 48 h, and exposed rats to high doses of fluoride (30 and 100 ppm) in their drinking water for 7 months. The expression of nAChRs at mRNA and protein levels, neurotoxicity and oxidative stress were analyzed in the study. The results indicated that there were no significant changes at mRNA level of the nAChR alpha3, alpha7, beta2 subunits in PC12 cells, and alpha4, alpha7, beta2 subunits in rat brains between the groups with fluorosis and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, and increased levels of protein oxidation and lipid peroxidation were observe in PC12 cells treated with high doses of fluoride or rat brains with chronic fluorosis.

The decreases of nAChR alpha3 and alpha7 subunit proteins in PC12 cells resulted from fluoride toxicity were mostly prevented by a pretreatment with antioxidant. The results suggest that the deficit of nAChRs induced by fluoride toxicity occurs at the level of post-transcription of the receptor gene, in which a mechanism might be involved in the damage by oxidative stress.


In this study, rats drinking fluoridated water for 7 months exhibited a decrease in “nicotinic acetylcholine receptors” (nAChRs) in their brains. The rats’ serum fluoride levels were comparable to that of humans living in fluoridated communities, and children who swallow fluoride toothpaste.

Dr. Agneta Nordberg, a Swedish neurotoxicologist and expert on nAChRs, has said:

“The [nAChRs] in the brain are important for functional processes, including cognitive and memory functions… The nAChRs are found to be involved in a complex range of central nervous system disorders including Alzheimer’s disease (AD), Parkinson’s disease, schizophrenia, Tourette’s syndrome, anxiety, depression, and epilepsy.”

The link between nAChRs and Alzheimer’s disease has been reported by Nordberg (Biological Psychiatry 2001; vol. 49; pp. 200-10).

A number of studies have linked fluoride with Alzheimer’s disease (Varner 1998, Strunecka 1999), reduced IQ (from 2000 – 2004 – eg Li, Xiang), and ADD/ADHD (Mullinex 1999).

The consistency between these studies is compelling evidence of fluoride’s neurotoxicity at levels of exposure in fluoridated communities.