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Abstract

Excess fluoride intake has been linked with various pathological conditions. The objective of the present study was to understand the role of fluoride in neurotoxic, neuroinflammatory, and neurodegenerative changes in the brain tissue of Wistar rats. Wistar rats were fed with water containing 20–100 ppm (ppm) sodium fluoride (NaF). An array of neurotransmitters (acetylcholine, dopamine, epinephrine, norepinephrine, serotonin, histamine, and glutamate) expression levels were estimated with respect to different fluoride concentrations. Additionally, its effect on the expression levels of specific neuroinflammatory markers (iNOS, COX-2, TNF-?, PKC, VEGF, and HSP-70) in brain tissues of Wister rats was assessed. An increase in NaF concentration resulted in increased fluoride deposition in the brain which in turn caused increase levels of epinephrine, histamine, serotonin, and glutamate and decreased levels of norepinephrine, acetylcholine, and dopamine in a dose-dependent manner. Tissue fluoride levels of the hippocampus, neocortex, cerebellum, spinal cord, and sciatic nerve increased significantly in fluoride fed rats. Transmission electron microscopy in the experimental animals revealed axon deterioration, myelin sheath degeneration, and dark cells with scanty cytoplasm in the spinal cord and sciatic nerve. Additionally, vacuolated swollen mitochondria were observed in the neocortex, hippocampus, and cerebellum. Results suggest excess fluoride intake modulates a set of biological marker and promote neuroinflammatory and neurodegenerative condition in Wister rats. Therefore, we conclude that the accumulation of NaF alters the neurological function which leads to neurodegenerative disorders.

*Original abstract online at https://link.springer.com/article/10.1007%2Fs12011-020-02362-x

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Acknowledgments

The authors would like to thank Prof. Pratap K. Reddy, Dr. Praveen K. Kumar, and the technical staff of Dept. of Zoology, Osmania University, Hyderabad, India, for their kind patronage. PYR would like to acknowledge the University Grants Commission for awarding Teacher Fellowship during the 10th plan period.

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All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

Corresponding author

Correspondence to Varun Kumar Sharma.

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The authors declare that they have no conflict of interest.

Ethics Approval

The study protocol was approved by the Animal Ethics committee (CPCSEA NO: 383/01/a/CPCSE) of the Department of Zoology, Osmania University, Hyderabad, India.