Intrauterine and Postnatal Exposure to High Levels of Fluoride Is Associated with Motor Impairments, Oxidative Stress, and Morphological Damage in the Cerebellum of Offspring Rats

Abstract

Fluoride (F) is abundantly present on Earth and plays a beneficial role in human health. However, exposure to high doses of F can be a risk, mainly in endemic fluorosis regions. In light of this, we investigated the effects of F exposure during the intrauterine and postnatal periods of rats, in doses similar to those recommended in drinking water and the levels of F in regions with endemic fluorosis, on the offspring rats’ cerebellum. Pregnant rats were divided into three groups: control (received ultrapure water only), 10 mg F/L, and 50 mg F/L for a period of 42 days (21 days gestation and 21 days lactation). At the end of the lactation period, the male pups were evaluated by behavioral tests, morphological markers, and biochemistry assays. The results pointed out that 50 mg F/L exposure during the intrauterine and lactational period of rats is capable of promoting oxidative stress in the cerebellum with a decrease in Purkinje cell density and myelin basic protein compromise, which could be associated with functional motor impairments. In addition, although 10 mg F/L exposure promoted redox alterations, it did not affect other parameters evaluated, highlighting the safe use of F in low doses.

Exploration of the SIRT1-mediated BDNF–TrkB signaling pathway in the mechanism of brain damage and learning and memory effects of fluorosis

“…Brain tissue is highly dependent on oxygen and rich in polyunsaturated fatty acids that are easily attacked by free radicals, which cause lipid peroxidation and oxidative stress damage ( 34 , 35 ). Fluorosis increased oxidative stress levels, which led to apoptosis, and the decreased learning and memory abilities of fluorosis rats were related to the increased oxidative stress levels ( 36 , 37 ). Therefore, the brain is the organ that receives the most obvious damage from free radicals during fluorosis.…”

A Scoping Review of Iodine and Fluoride in Pregnancy in Relation to Maternal Thyroid Function and Offspring Neurodevelopment

“…In attempting to explain the relationship between F exposure during pregnancy and IQ, preclinical studies of F exposure during pregnancy have focused on the effects of high levels of F exposure on offspring growth and neurodevelopment. Excessive F exposure decreases the food consumption and weight gain in the mother whereas in the offspring, growth ( in utero and postnatal) [ 117 ], brain weight [ 15 ], and hippocampal [ 15 , [118] , [119] , [120] , [121] , [122] , [123] ] as well as cerebellum [ 124 ] neurons are adversely affected. Attention, sensory and motor development were also reported to be affected in the study by Bartos et al.…”

“… Souza-Monteiro et al. [ 124 ] Animal (Wistar rat) model N/A Pregnant rats were divided into 3 groups, 10 mg/L fluoride, 50 mg/L fluoride, and a control group for 21 d prenatally and day 21 postpartum. Male offspring were evaluated at day 21 d postpartum.…”

The Effect of Prenatal and Neonatal Fluoride Exposure to Morphine-Induced Neuroinflammation

“…Although the mechanisms of fluoride neurotoxicity are still not well understood, it is known that the element contributes to the induction of oxidative stress and leads to neuronal apoptosis [26,28]. It may contribute to the development of neuroinflammation and neurodegenerative changes in the striata, motor cortices, cerebella, and amygdalae of rats [26,[29][30][31].…”

“…Currently, there is no information in the literature regarding the impact of fluoride-induced inflammation in pre-and neonatal period on the development of morphine dependence. The neurodegenerative and neuroinflammatory properties of this element affecting the mesolimbic and mesocortical systems suggest that this element may influence the development of dependence [27,29,31]. Our study aims to evaluate the inflammatory state of selected brain structures in morphine-dependent rats pre-exposed to fluoride.…”