Abstract
Using Sprague-Dawley rats and rat PC12 cells treated with sodium fluoride (NaF), we investigated the effects of SIK2-CRTC1 signaling on the neurobehavioral toxicity induced by fluoride. The in vivo results demonstrated that NaF treatment induced anxiety- and depression-like behaviors in juvenile rats, resulting in histological and ultrastructural abnormalities in the rat hippocampus and medial prefrontal cortex. Moreover, NaF exposure induced neuronal loss and excessive apoptosis. We also found that NaF elevated the expression of SIK2 and reduced the expression of CRTC1, brain-derived neurotrophic factor (BDNF), and VGF. The in vitro results showed that NaF suppressed cell viability, induced SIK2-CRTC1 signaling dysfunction, and caused excessive apoptosis in PC12 cells. Notably, targeted knockout of SIK2 with SIK2-siRNA or blocking of SIK2-CRTC1 signaling with 7,8-dihydroxyflavone (7,8-DHF) (as well as venlafaxine) can reduce apoptosis and increase cell viability in vitro. These findings suggest that neuronal death resulting from abnormal SIK2-CRTC1 signaling contributes to neurobehavioral toxicity induced by fluoride.
Graphical Abstract
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Effects of chronic fluorosis on the brain.
Highlights Reviewing the mechanism of brain injury caused by chronic fluorosis is of great significance for protecting residents in fluorosis endemic areas. Abstract This article reviews the effects of chronic fluorosis on the brain and possible mechanisms. We used PubMed, Medline and Cochraine databases to collect data on fluorosis, brain injury,
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Fluoride-induced neuron apoptosis and expressions of inflammatory factors by activating microglia in rat brain
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
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Effects of NaF on the expression of intracellular Ca2+ fluxes and apoptosis and the antagonism of taurine in murine neuron
Sodium fluoride (NaF) has been shown to be cytotoxic and produces inflammatory responses in humans. However, the cellular mechanisms underlying the neurotoxicity of fluoride are unclear. The present study aims to define a possible mechanism of NaF-induced neurotoxicity with respect to apoptosis and intracellular Ca(2+) fluxes. Meanwhile, the cytoprotective role
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The Effect of Chronic Fluorosis on Calcium Ions and CaMKIIa, and c-fos Expression in the Rat Hippocampus.
This study investigated neurotoxicity of chronic fluorosis in the rat hippocampus. Newly weaning, male, Sprague-Dawley (SD) rats were administered 15, 30, and 60 mg/L sodium fluoride (NaF) solution (fluorine ion concentration 8.25, 16.50, and 33.00 mg/L, respectively), and tap water, for 18 months. The neurotoxicological mechanism was examined with a focus on intracellular
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Effect of dexmedetomidine on sevoflurane-induced neurodegeneration in neonatal rats.
Background: Structural brain abnormalities in newborn animals after prolonged exposure to all routinely used general anaesthetics have raised substantial concerns for similar effects occurring in millions of children undergoing surgeries annually. Combining a general anaesthetic with non-injurious sedatives may provide a safer anaesthetic technique. We tested dexmedetomidine as a mitigating
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NRC (2006): Fluoride's Neurotoxicity and Neurobehavioral Effects
The NRC's analysis on fluoride and the brain.
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Fluoride: Developmental Neurotoxicity.
Developmental Neurotoxicity There has been a tremendous amount of research done on the association of exposure to fluoride with developmental neurotoxicity. There are over 60 studies reporting reduced IQ in children and several on the impaired learning/memory in animals. And there are studies which link fluoride to Attention Deficit Hyperactivity Disorder. Teaching
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Fluoride & IQ: 76 Studies
• As of July 18, 2022, a total of 85 human studies have investigated the relationship between fluoride and human intelligence. • Of these investigations, 76 studies have reported that elevated fluoride exposure is associated with reduced IQ in humans. • The studies which reported an association of reduced IQ with exposure
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Fluoride Affects Learning & Memory in Animals
An association between elevated fluoride exposure and reduced intelligence has now been observed in 65 IQ studies. 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 45 studies (out
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Fluoride's Direct Effects on Brain: Animal Studies
The possibility that fluoride ingestion may impair intelligence and other indices of neurological function is supported by a vast body of animal research, including over 40 studies that have investigated fluoride's effects on brain quality in animals. As discussed by the National Research Council, the studies have consistently demonstrated that fluoride, at widely varying concentrations, is toxic to the brain.
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