Low Glucose Utilization and Neurodegenerative Changes Caused by Sodium Fluoride Exposure in Rat’s Developmental Brain

Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhi‐Zhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Lü, Yang; Yi-hu, Chen; Wu, Xue; Zhang, Xiaofei; Yu, Linyu; Wang, Aiguo

doi:10.1007/s12017-013-8260-z

Cited by 59 publications

(46 citation statements)

References 47 publications

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“…Bars were presented as mean±SD. *p<0.05 compared to control group, **p<0.01 compared to control group Discussion A number of studies reported neuropathological lesions in chronic and high dose of fluoride treated brain, such as chromatolysis of Purkinje neurons, damage to the neurons and neuroglial cells, and neurodegenerative changes in rat brain [17]. However, the molecular mechanism underlying the pathogenesis of CNS damage induced by chronic fluorosis remains elusive.…”

Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 90%

“…However, a high level of IL-1β can profoundly impair memory and is associated with neurodegenerative disorders [46,47]. The developmental neurotoxicity of fluoride may be closely associated with neurodegenerative changes [17]. The suppression of the inflammatory activation of microglia might play a part in ameliorated cognitive deficits [48].…”

Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 99%

“…Microglia activation is a key causative factor in neurodegeneration [49]. NaF-treated rat displayed neurodegenerative changes [17]. Neurodegeneration initiated by microglia can be driven through TNF-α signaling [50].…”

Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 99%

“…Chronic or subchronic fluoride exposure may lead to reduction of acetylcholinesterase activity and nicotinic acetylcholine receptor level, as well as alteration in the neurotransmitter level [15,16]. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes [17]. The hippocampus is the key region for learning and memory in the brain and has been postulated to be one of the neurotoxic target sites attacked by fluoride [18].…”

Section: Introductionmentioning

confidence: 99%

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Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Yan

Liu

et al. 2015

Mol Neurobiol

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Excessive exposure to fluoride results in structural and functional damages to the central nervous system (CNS), and neurotoxicity of fluoride may be associated with neurodegenerative changes. Chronic microglial activation appears to cause neuronal damage through producing proinflammatory cytokines and is involved in many neurodegenerative disorders. It is not known about effects on microglia of fluoride. In the present study, healthy adult Wistar rats were exposed to 60 and 120 ppm fluoride in drinking water for 10 weeks, and control rats received deionized water. After 10 weeks, rats were sacrificed under anesthesia then apoptosis in neuron and inflammatory factors secreted by microglia were determined. We found that apoptosis of neurons in fluoride-treated rat brain increased and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive immunofluorescence increased with increasing fluoride concentrations. Bax protein expression increased and Bcl-2 protein expression decreased in fluoride-treated rat brain compared with that of the control rat brain. The microglia in the hippocampus and cortex of fluoride-treated rats were activated by immunostaining with OX-42, a marker of activated microglia, and OX-42-positive microglia cells were more abundant in the hippocampus than in the cortex. The levels of IL-1β and IL-6 protein expression in OX-42-labeled microglial cells were significantly increased in the cortex and hippocampus of rats exposed to fluoride, and TNF-α immunoreactivity in microglial cells of the hippocampus was significantly higher in the 120 ppm fluoride-treated group than that in the control group. Our results indicate that fluoride induced neuron apoptosis and expressions of inflammatory factors by activating microglia in rat brain.

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Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 90%

Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 99%

Section: Effects Of Fluoride On the Inflammatory Factor Expressions Imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Yan

Liu

et al. 2015

Mol Neurobiol

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“…This may account for increased blood glucose levels in fluoride intoxicated animals (Garzia-Montalvo et al 2009); and (3) developmental fluoride exposure causes neuronal degeneration, decreased brain glucose utilization, and decreased the protein expression of GLUT 1 with concomitant impairment in learning and memory through adulthood (Jiang et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues

et al. 2017

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The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

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Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada

et al. 2019

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IMPORTANCE The potential neurotoxicity associated with exposure to fluoride, which has generated controversy about community water fluoridation, remains unclear. OBJECTIVE To examine the association between fluoride exposure during pregnancy and IQ scores in a prospective birth cohort. DESIGN, SETTING, AND PARTICIPANTS This prospective, multicenter birth cohort study used information from the Maternal-Infant Research on Environmental Chemicals cohort. Children were born between 2008 and 2012; 41% lived in communities supplied with fluoridated municipal water. The study sample included 601 mother-child pairs recruited from 6 major cities in Canada; children were between ages 3 and 4 years at testing. Data were analyzed between March 2017 and January 2019. EXPOSURES Maternal urinary fluoride (MUF SG), adjusted for specific gravity and averaged across 3 trimesters available for 512 pregnant women, as well as self-reported maternal daily fluoride intake from water and beverage consumption available for 400 pregnant women. MAIN OUTCOMES AND MEASURES Children's IQ was assessed at ages 3 to 4 years using the Wechsler Primary and Preschool Scale of Intelligence-III. Multiple linear regression analyses were used to examine covariate-adjusted associations between each fluoride exposure measure and IQ score. RESULTS Of 512 mother-child pairs, the mean (SD) age for enrollment for mothers was 32.3 (5.1) years, 463 (90%) were white, and 264 children (52%) were female. Data on MUF SG concentrations, IQ scores, and complete covariates were available for 512 mother-child pairs; data on maternal fluoride intake and children's IQ were available for 400 of 601 mother-child pairs. Women living in areas with fluoridated tap water (n = 141) compared with nonfluoridated water (n = 228) had significantly higher mean (SD) MUF SG concentrations (0.69 [0.42] mg/L vs 0.40 [0.27] mg/L; P = .001; to convert to millimoles per liter, multiply by 0.05263) and fluoride intake levels (0.93 [0.43] vs 0.30 [0.26] mg of fluoride per day; P = .001). Children had mean (SD) Full Scale IQ scores of 107.16 (13.26), range 52-143, with girls showing significantly higher mean (SD) scores than boys: 109.56 (11.96) vs 104.61 (14.09); P = .001. There was a significant interaction (P = .02) between child sex and MUF SG (6.89; 95% CI, 0.96-12.82) indicating a differential association between boys and girls. A 1-mg/L increase in MUF SG was associated with a 4.49-point lower IQ score (95% CI, −8.38 to −0.60) in boys, but there was no statistically significant association with IQ scores in girls (B = 2.40; 95% CI, −2.53 to 7.33). A 1-mg higher daily intake of fluoride among pregnant women was associated with a 3.66 lower IQ score (95% CI, −7.16 to −0.14) in boys and girls. CONCLUSIONS AND RELEVANCE In this study, maternal exposure to higher levels of fluoride during pregnancy was associated with lower IQ scores in children aged 3 to 4 years. These findings indicate the possible need to reduce fluoride intake during pregnancy.

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Low Glucose Utilization and Neurodegenerative Changes Caused by Sodium Fluoride Exposure in Rat’s Developmental Brain

Cited by 59 publications

References 47 publications

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Fluoride-Induced Neuron Apoptosis and Expressions of Inflammatory Factors by Activating Microglia in Rat Brain

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues

Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada

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