Fluoride Action Network

Fluoride Affects Learning & Memory in Animals

Fluoride Action Network | August 2012 | By Michael Connett (UPDATED November 16, 2014)
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  • An association between elevated fluoride exposure and reduced intelligence has now been observed in over 30 studies of human populations. Although a link between fluoride and intelligence might initially seem surprising or random, it is actually consistent with a large body of animal research. This animal research includes the following 30 studies where mice or rats treated with fluoride were found to suffer impairments in their learning and/or memory abilities. Although two animal studies have failed to find this association, (Whitford 2009; Varner 1994), the clear majority of both animal and human research indicates that fluoride can damage cognitive function.

    Studies Finding an Effect on Learning ANd/or Memory

    “The behavior tests showed that 56 days of fluoride and lead administration significantly reduced the vertical activity and lowered the memory ability of mice..”
    SOURCE: Niu R, et al. (2014). Proteomic analysis of hippocampus in offspring male mice exposed to fluoride and lead. Biological Trace Element Research [Epub ahead of print[.

    “These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus.”
    SOURCE: Jiang S, et al. (2014). Fluoride and Arsenic Exposure Impairs Learning and Memory and Decreases mGluR5 Expression in the Hippocampus and Cortex in Rats. PLoS One. 2014 Apr 23;9(4):e96041.

    “Taken together, these results indicated that long-term fluoride administration can enhance the excitement of male mice, impair recognition memory, and upregulate VAMP-2 mRNA expression, which are involved in the adverse effects of fluoride on the object recognition memory of nervous system.”
    SOURCE: Han H, et al. (2014). Effects of chronic fluoride exposure on object recognition memory and mRNA expression of SNARE complex in hippocampus of male mice. Biological Trace Element Research [Epub ahead of print]

    “Collectively, our data indicate that developmental exposure to NaF induces cognitive deficits and anxiety-depression-like behaviors in mice.”
    SOURCE: Liu F, et al. (2014). Fluoride exposure during development affects both cognition and emotion in mice. Physiology & Behavior 124:1-7.

    “We found that NaF treatment impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride
    may be closely associated with low glucose utilization and neurodegenerative changes.”
    SOURCE: Jiang C, et al. (2014). Low Glucose Utilization and Neurodegenerative Changes Caused by Sodium Fluoride Exposure in Rat’s Developmental Brain. Neuromolecular Medicine 16(1):94-105.

    “The results of the present study showed no behavioural deficits in the control group of animals however, the rats that received fluoride water exhibited impairment in their spatial learning and memory deficits. The deficits are not marked in the vitamin C and G. biloba groups. To conclude chronic exposure to high levels of fluoride causes severe impairment in the spatial learning and memory, these deficits can be ameliorated with the vitamin C and G. biloba.”
    SOURCE: Jetti R, et al. (2013). Protective effect of ascorbic acid and Ginkgo biloba against learning and memory deficits caused by fluoride. Toxicology and Industrial Health. 2013 Sep 30. [Epub ahead of print]

    “The Y-maze test has been widely used to evaluate cognitive abilities. The test involves recording the CRT [correct reaction time]. . . .  The CRT of the NaF group on the 9th day decreased significantly (p<0.01, vs. control group). The CRT of the rats treated with EGb [ginko bilboa extract] significantly increased compared to the rats that received fluoride and saline (p<0.01). After 2 weeks, the Y-maze test was performed again to test the CRT. As showed in Fig. 1c, the CRT of the EGb group was significantly more than that of the NaF group (p<0.01). This result suggested that EGb could improve learning and memory impairment induced by chronic fluoride exposure in rats.”
    SOURCE: Zhang C, et al. (2013). The analog of ginkgo biloba extract 761 is a protective factor of cognitive impairment induced by chronic fluorosis.Biological Trace Element Research 153:229-36.

    “The learning and memory abilities were lower in chronic fluorosis groups, particularly in medium and high fluorosis groups (P <0.05 or P <0.01) than in the normal group. Compared with the normal group, marked morphological changes were observed in the hippocampal cells in high fluorosis group. Conclusion: The rat model has a strong resemblance in cognitive dysfunction caused by chronic fluorosis to that in population of high fluorosis areas . . . .”
    SOURCE: Chen H, Deng G. (2012). [The establishment and assessment of animal model of chronic fluorosis-induced cognitive dysfunction in rats]. Acta Academiae Medicinae Xuzhou 31(5):319-22.

    “In this study F-toxicated animals took more time (seconds) to reach the goal area (latency) and committed more number of errors during the criteria leading to a less number of correct choices (performance), subsequently more number of sessions were conducted to learn the task (acquisition) in T maze test. This impaired spatial memory performance might be due to F accumulation (retention) in brain areas especially in hippocampus, which triggered oxidative stress to higher fold contributing to cognitive deficits.”
    SOURCE: Basha PM, Sujitha NS (2012). Combined impact of exercise and temperature in learning and memory performance of fluoride toxicated rats. Biological Trace Element Research 150:306-13.

    “NaF induced motor incoordination, depression, and memory impairment, and these were prevented by coadministration of BM in mice.”
    SOURCE: Balaji B, et al. (2012). Evaluation of standardized Bacopa monniera extract in sodium fluoride induced behavioural, biochemical, and histopathological alterations in mice. Toxicology and Industrial Health. 2012 Dec 6. [Epub ahead of print]

    “The results demonstrate that fluoride exposure may develop an adverse effect on the learning capacity of rats, this may be caused by monoamine neurotransmitters levels alteration.”
    SOURCE: Zhu Y, et al. (2012). Effects of fluoride exposure on performance in water labyrinth and monoamine neurotransmitters of rats. Journal of Xinjiang Medical University 35(3):330-33.

    “The results showed that NaF impairs open-field habituation and increases noradrenaline (NA) and serotonin (5-HT) in the striatum, hippocampus and neocortex. Dopamine (DA) increase was restricted to the striatum. Short-term NaF withdrawal did not reverse these NaF-induced changes, and both NaF treatments led to a mild fluorosis in rat incisors. No treatment effect was seen in body weight or fluid/water consumption. These results indicate that sodium fluoride induces memory impairment that outlasts short-term NaF withdrawal (2 weeks) and may be associated with NA and 5-HT increases in discrete brain regions.”
    SOURCE: Pereira M, et al. (2011). Memory impairment induced by sodium fluoride is associated with changes in brain monoamine levels. Neurotox Res. 19(1):55-62.

    “In the T-maze experiments, the fluoride-treated group showed poor acquisition and retention and higher latency when compared with the control. The alterations were more profound in the third generation when compared with the first- and second-generation fluoride-treated group. Changes in the thyroid hormone levels in the present study might have imbalanced the oxidant/antioxidant system, which further led to a reduction in learning memory ability. Hence, presence of generational or cumulative effects of fluoride on the development of the offspring when it is ingested continuously through multiple generations is evident from the present study.”
    SOURCE: Basha PM, et al. (2011). Fluoride toxicity and status of serum thyroid hormones, brain histopathology, and learning memory in rats: a multigenerational assessment. Biol Trace Elem Res. 144(1-3):1083-94.

    “The results showed that in the rat offspring exposed to higher fluoride as compared to controls, the learning and memory ability declined; the cholinesterase activities in the brains were inhibited; the protein levels of alpha3, alpha4 and alpha7 nAChR subunits were decreased which showed certain significant correlations with the declined learning and memory ability; and the mRNA levels of alpha3 and alpha4 nAChRs were decreased, whereas the alpha7 mRNA increased.”
    SOURCE: Gui CZ, et al. (2010). Changes of learning and memory ability and brain nicotinic receptors of rat offspring with coal burning fluorosis. Neurotoxicol Teratol. 32(5):536-41.

    “Our results suggest that exposure of rats to Na-F in high doses for long duration has detrimental effects on the brain as reflected in diminished learning and memory.”
    SOURCE: El-Lethey H, et al. (2010). Neurobehavioral toxicity produced by sodium fluoride in drinking water of laboratory rats. Journal of American Science 6:54-63

    “The results showed that as compared with controls, the learning and memory capacity in the rats with fluorosis was decreased. The protein expressions of alpha7 and alpha4 nAChR subunits in rat brains with fluorosis were decreased by 35% and 33%, whereas the corresponding receptor subunit mRNAs did not exhibit any changes. The increases of phospho- and total-ERK1/2 as well as phospho-MEK1/2 at the protein levels were found in the brains of rats with fluorosis as compared to controls, and no difference of ERK1/2 mRNA was found. In addition, the activation rate of phospho-ERK1/2 was decreased in the brains affected with fluorosis. The modifications of nAChRs and ERK1/2 pathway might be connected with the molecular mechanisms in the decreased capacity of learning and memory of the rats with fluorosis.”
    SOURCE: Liu YJ, et al. (2010). Alterations of nAChRs and ERK1/2 in the brains of rats with chronic fluorosis and their connections with the decreased capacity of learning and memory. Toxicol Lett. 192(3):324-9.

    “Conclusion: Brick tea fluoride and aluminum poisoning of rats obstructs learning and memory and brain tissue SS expression decreases.”
    SOURCE: Bai J, et al. (2010). Learning and memory obstacles and changes in brain tissue growth inhibitors from brick tea fluoride and aluminum poisoning of rats. Chinese Journal of Control of Endemic Diseases 25(3):161-63.

    “The aim of this research was to study the mechanism of the decreased learning and memory of rats with chronic fluorosis. Compared with controls, decreased learning and memory ability, lower levels of total antioxidant capacity (TAOC), and increased content of malondialdehyde (MDA) in brain tissues were observed in both male and female young adult rats after 6 months with either 5 or 50 mg NaF/L in their drinking water. . . . The results indicate that the reduced learning capacity and memory ability of rats induced by F may be connected with increased oxidative stress and diminished cholinergic nervous system responses.”
    SOURCE: Gao Q, et al. (2009). Decreased learning and memory ability in rats with fluorosis: increased oxidative stress and reduced cholinesterase activity in the brain. Fluoride 42(4):277-85.

    “Objective: To explore the effects of fluoride in learning and memory changes and the antagonism of selenium by way of animal experiments. . . . Conclusion: Fluoride can damage the learning and memory function, and selenium may [mitigate these] effects.”
    SOURCE: Gao Y, et al. (2009). [Effects of learning and memory of fluoride and the antagonism of selenium in rat.] [Study in Chinese] Studies of Trace Elements and Health 26(2).

    “Conclusion: Passing through placental barriers, the fluorine exposure of pregnant rats can have a certain effect on the learning and memory capabilities of baby rats, and it may be related to SOD activity and MDA content in the brain.”
    SOURCE: Zhang J, et al. (2009). The effect of fluorine exposure of pregnant rats on the learning and memory capabilities of baby rats. Chinese Journal of Public Health 25(11):1347-48.

    “Results showed that the learning abilities and hippocampus glutamate levels were significantly decreased by [fluoride] and [lead] individually and the combined interaction of [fluoride] and [lead]. . . . These findings suggested that alteration of hippocampus glutamate by [fluoride] and/or [lead] may in part reduce learning ability in rats.”
    SOURCE: Niu R, et al. (2009). Decreased learning ability and low hippocampus glutamate in offspring rats exposed to fluoride and lead. Environ Toxicol Pharmacol. 28(2):254-8.

    “Overall, these results suggest that moderate intoxication with sodium fluoride has potentially deleterious effects on learning and memory.”
    SOURCE: Chioca LR, et al. (2008). Subchronic fluoride intake induces impairment in habituation and active avoidance tasks in rats. European Journal of Pharmacology 579(1-3):196-201.

    “Conclusion: The results indicate that chronic fluorosis has a significant effect on rat learning and memory behavior.”
    SOURCE: Wang G, et al. (2006). Effect of different doses of chronic exposure of fluoride on rat learning and memory behavior. Studies of Trace Elements & Health 23(2):1-2.

    “Objective: To study the effect of high level fluoride and low level iodine on learning-memory in offspring rats and possible mechanism. . . . Results: Compared with control rats, error number (EN1) and (EN2) of the experimental offspring rats increased significantly (P0.05). Sustaining time (ST) reduced obviously (P0.05). EN1 and EN2 of the experimental rats in the group of high fluoride and low iodine were the highest in all groups (P0.05)..”
    SOURCE:  Hong J, et al. (2005). [Effects of high fluoride and low iodine on learning-memory and TchE of brain in offspring rats]. China Preventive Medicine. Available online at: http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZGYC200506000.htm

    “In comparison with control rats, the learning and memory ability of the offspring rats was depressed by high fluoride, low iodine, or the combination of high fluoride and low iodine.”
    SOURCE: Wang J, et al. (2004). Effects of high fluoride and low iodine on biochemical indexes of the brain and learning-memory of offspring rats. Fluoride 37: 201-208.

    “The learning memory abilities of rats in high F group, high I-high F group, and low I-high F group were significantly lower than control group, while the learning memory abilities of rats given proper concentration I and Se increased significantly.”
    SOURCE: Shen X, et al. (2004). [Effect of iodine and selenium on learning memory impairment induced by fluorosis and blood biochemical criterion of rats]. Occupation & Health 20(1):6-8.

    “Fluoride intoxicated animals also performed poorly in motor co-ordination tests and maze tests. Inability to perform well increased with higher fluoride concentration in drinking water.”
    SOURCE: Bhatnagar M, et al. (2002). Neurotoxicity of fluoride: neurodegeneration in hippocampus of female mice. Indian Journal of Experimental Biology 40: 546-54.

    “Conclusion: Fluorosis of mice caused significant harm to some open field behavior and learning capabilities of mice, there was a certain effect on brain SOD activity, and this effect may have a certain relation to the fluoride concentration.”
    SOURCE: Xu X, et al. (2001). Effect of fluorosis on mice learning and memory behaviors and brain SOD activity and MDA content. China Public Health 17(1):8-10.

    “The main results showed that the learning capability of mice drinking higher concentration of fluoride presented remarkable deterioration.”
    SOURCE: Zhang Z, et al. (2001). Effects of selenium on the damage of learning-memory ability of mice induced by fluoride. [Article in Chinese] Journal of Hygiene Research 30(3):144-146.

    “Learning and memory abilities of high-fluoride exposed groups were significantly lower than that of the control group, while the brain ChE activities of high-fluoride exposed groups were significantly higher. Conclusions: High fluoride concentration in drinking water can decrease the cerebral functions of mice. Fluoride is a neurotoxicant.”
    SOURCE: Sun ZR, et al. (2000). Effects of high fluoride drinking water on the cerebral functions of mice. Chinese Journal of Epidemiology 19: 262-263.

    “The main results are as follows: the learning ability of mice drinking high concentration of fluoride presented remarkable deterioration… The results suggested that the impairment on the learning capability induced by fluorosis may be closely related with the pathological changes of synaptic structure in the brain of mice.”
    SOURCE: Zhang Z, et al. (1999). Effect of fluoride exposure on synaptic structure of brain areas related to learning-memory in mice. Journal of Hygiene Research 28(4):210-2. (Republished in Fluoride 2008; 41:139-43.

    See also:

    “This is the first laboratory study to demonstrate that CNS functional output is vulnerable to fluoride, that the effects on behavior depend on the age at exposure and that fluoride accumulates in brain tissues. Experience with other developmental neurotoxicants prompts expectations that changes in behavioral function will be comparable across species, especially humans and rats. Of course behaviors per se do not extrapolate, but a generic behavioral pattern disruption as found in this rat study can be indicative of a potential for motor dysfunction, IQ deficits, and/or learning disabilities in humans.”
    SOURCE: Mullenix P, et al. (1995). Neurotoxicity of Sodium Fluoride in Rats. Neurotoxicology and Teratology 17(2):169-177.