The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System

Abstract

Fluorides occur naturally in the environment, the daily exposure of human organism to fluorine mainly depends on the intake of this element with drinking water and it is connected with the geographical region. In some countries, we can observe the endemic fluorosis—the damage of hard and soft tissues caused by the excessive intake of fluorine. Recent studies showed that fluorine is toxic to the central nervous system (CNS). There are several known mechanisms which lead to structural brain damage caused by the excessive intake of fluorine. This element is able to cross the blood-brain barrier, and it accumulates in neurons affecting cytological changes, cell activity and ion transport (e.g. chlorine transport). Additionally, fluorine changes the concentration of non-enzymatic advanced glycation end products (AGEs), the metabolism of neurotransmitters (influencing mainly glutamatergic neurotransmission) and the energy metabolism of neurons by the impaired glucose transporter—GLUT1. It can also change activity and lead to dysfunction of important proteins which are part of the respiratory chain. Fluorine also affects oxidative stress, glial activation and inflammation in the CNS which leads to neurodegeneration. All of those changes lead to abnormal cell differentiation and the activation of apoptosis through the changes in the expression of neural cell adhesion molecules (NCAM), glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and MAP kinases. Excessive exposure to this element can cause harmful effects such as permanent damage of all brain structures, impaired learning ability, memory dysfunction and behavioural problems. This paper provides an overview of the fluoride neurotoxicity in juveniles and adults.

The potential roles of aluminum chloride and sodium fluoride on the neurotoxicity of the cerebral cortex, hippocampus, and hypothalamus of male rat offspring

“…These results may be explained by delay in the neuro-maturation of the monoaminergic systems and/or imbalance between the synthesis and degradation of these monoamines (El-Habibi, Mousa, & Mohamed, 2011;Pereira, Dombrowski, Losso, Chioca, Da Cunha, & Andreatini, 2011). It has been shown that exposure to aluminum/sodium fluoride during the gestational and lactational periods induced persistent neurobehavioral deficits in the offspring due to the ability of aluminum and fluoride to transport through the placental barrier and to cross the blood-brain barrier (Dec et al, 2017;Panchal & Verma, 2014;World Health Organization, 1996). Moreover, fluorine was found to induce deregulation in the secretion of serotonin, dopamine, norepinephrine, acetylcholine, and epinephrine in the hippocampus, striatum, and cerebral cortex (Dec et al, 2017).…”

“…It has been shown that exposure to aluminum/sodium fluoride during the gestational and lactational periods induced persistent neurobehavioral deficits in the offspring due to the ability of aluminum and fluoride to transport through the placental barrier and to cross the blood-brain barrier (Dec et al, 2017;Panchal & Verma, 2014;World Health Organization, 1996). Moreover, fluorine was found to induce deregulation in the secretion of serotonin, dopamine, norepinephrine, acetylcholine, and epinephrine in the hippocampus, striatum, and cerebral cortex (Dec et al, 2017). In this regard, it was reported that the potential implications of aluminum in the etiopathogenesis of neurological disorders were attributed, at least in part, to its inhibitory effect on the activity of dopamine-beta-hydroxylase (Milanese, Lkhayat, & Zatta, 2001).…”

Progressive Research in the Molecular Mechanisms of Chronic Fluorosis

“…In recent years, many studies have focused on fluorine neurotoxicity. The central nervous system during development is highly sensitive to the influence of fluorine due to its weakened protective mechanisms [66]. Studies showed that children in high fluoride areas had significantly lower IQ (intelligence quotient) scores than those who lived in low fluoride areas [67,68].…”

“…Fluorine causes glial cell activation which is involved in inflammation through producing proinflammatory cytokines. Chronic inflammation in the brain appears to cause neuronal damage [66,75]. Moreover, fluorine influences the synthesis of neurotransmitters, the activity of enzymes, the expression of receptors, and the plasticity of neurons [76][77][78].…”

“…Of note, because fluoride can not only cross the blood-brain barrier, but also penetrate through the placenta, fluorine exposure in the prenatal and neonatal periods is dangerous [66,79]. A recent study showed that during pregnancy and lactation, even at very low concentrations, F exposure may alter parameters of the central nervous system functionality, producing a delay in eye-opening development in the offspring as well as hypoactivity in adult offspring [80].…”