Fluoride-Induced Expression of Neuroinflammatory Markers and Neurophysiological Regulation in the Brain of Wistar Rat Mo

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Fluoride-Induced Expression of Neuroinflammatory Markers and Neurophysiological Regulation in the Brain of Wistar Rat Model Yugandhar P. Reddy 1,2 & Santosh Tiwari 3 & Lomas K. Tomar 4 & Nalini Desai 2 & Varun Kumar Sharma 3,4 Received: 17 June 2020 / Accepted: 25 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

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-α, 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. Keywords Sodium fluoride . Neurotoxic effects . Neurodegenerative effects . Neuroinflammation . Wistar rats

Introduction Fluoride plays an important role in the developmental process; however, excess fluoride intake is reported to adversely affect neurological functioning [1–3]. Moreover, evidence from other studies have reported significant histological changes during the early development stages in experimental models

* Varun Kumar Sharma [email protected] 1

Neurobiology Laboratory, Department of Zoology, University College of Sciences, Osmania University, Hyderabad, Telangana, India

2

Department of Zoology, The Adoni Arts and Science College, Adoni, Kurnool, Andhra Pradesh, India

3

Center for Liver Research and Diagnostics, Deccan College of Medical Sciences Kanchanbagh, Hyderabad, Telangana, India

4

Department of Biotechnology & Microbiology, School of Sciences, Noida International University, Sector-17 A, Yamuna Expressway, Gautam Budh Nagar, Uttar Pradesh 201308