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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Impaired V-ATPase leads to increased lysosomal pH, results in disrupted lysosomal degradation and autophagic flux blockage, contributes to fluoride-induced developmental neurotoxicity.
Highlights NaF exposure caused developmental neurotoxicity. NaF-induced neuronal apoptosis results from autophagic flux blockage. Raised lysosomal pH disrupting lysosomal degradation caused autophagic flux blockage. V-ATPase is a crucial factor regulating neuronal lysosomal pH. Upregulation of V-ATPase alleviate NaF-induced developmental neurotoxicity. Fluoride is capable of inducing developmental neurotoxicity, yet its mechanisms
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Rutin attenuates neurobehavioral deficits, oxidative stress, neuro-inflammation and apoptosis in fluoride treated rats.
Highlights The influence of rutin on fluoride – induced neurotoxicity in rat was studied. Rutin reversed the fluoride – induced neurobehavioral deficits in rats. Rutin reversed the fluoride – induced inhibition of acetylcholinesterase activity in rat cerebrum and striatum. Rutin enhanced antioxidant status and inhibited neuro-inflammation and apoptosis in fluoride
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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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Roles of mitochondrial fission inhibition in developmental fluoride neurotoxicity: mechanisms of action in vitro and associations with cognition in rats and children.
Fluoride neurotoxicity is associated with mitochondrial disruption. Mitochondrial fission/fusion dynamics is crucial to maintain functional mitochondria, yet little is known about how fluoride perturbs this dynamics and whether such perturbation contributes to impaired neurodevelopment. Here in human neuroblastoma SH-SY5Y cells treated with sodium fluoride (NaF, 20, 40 and 60 mg/L), mitochondrial
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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 78 studies reporting reduced IQ (75 studies with children and 3 studies with adults) and several on the impaired learning/memory in animals. And there are studies which link
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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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Fluoride's Effect on Fetal Brain
The human placenta does not prevent the passage of fluoride from a pregnant mother's bloodstream to the fetus. As a result, a fetus can be harmed by fluoride ingested pregnancy. Based on research from China, the fetal brain is one of the organs susceptible to fluoride poisoning. As highlighted by the excerpts
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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 & IQ: 76 Studies
Note: See the Updated list of fluoride IQ studies at https://fluoridealert.org/researchers/fluoride-iq-studies/the-fluoride-iq-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
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