Gestational exposure to fluoride impairs cognition in C57 BL/6 J male offspring mice via the p-Creb1-BDNF-TrkB signaling pathway

Li, Weisheng; Lu, Likui; Zhu, Dan; Liu, Jingliu; Shi, Yajun; Zeng, Hongtao; Xi, Yu; Guo, Jun; Wei, Bin; Cai, Yongle; Sun, Miao

doi:10.1016/j.ecoenv.2022.113682

Cited by 11 publications

(4 citation statements)

References 34 publications

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“…Furthermore, alterations in glutamate pathways have been implicated in the cause and treatment of anxiety disorders . Prenatal fluoride exposure may also adversely affect neurodevelopment and cognition by causing mitochondrial dysfunction which can increase oxidative stress, blocking autophagosome-lysosome fusion which can contribute to cellular damage, and by causing synaptic dysfunction . Additionally, prenatal fluoride exposure, even at low levels, can suppress maternal thyroid gland activity which can contribute to cognitive and neurobehavioral problems in offspring …”

Section: Discussionmentioning

confidence: 99%

Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months

Malin,

Eckel,

et al. 2024

JAMA Netw Open

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ImportanceRecent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown.ObjectiveTo examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US.Design, Setting, and ParticipantsThis prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks’ gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024.ExposureSpecific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure.Main Outcomes and MeasuresNeurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted.ResultsA total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02).Conclusions and RelevanceIn this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

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Section: Discussionmentioning

confidence: 99%

Maternal Urinary Fluoride and Child Neurobehavior at Age 36 Months

Malin,

Eckel,

et al. 2024

JAMA Netw Open

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“…Paraffin-embedded sections of the spleen, lungs, and jejunum were made according to the method of Liu et al, while hippocampal sections were made according to the method of Lu et al, and all were stained with HE. And paraffin-embedded sections of the hippocampus were subjected to Nissl staining, referring to the previous method of Lu et al and Li et al , The tissue morphology and pathological changes were observed using the ECHO revolve FL forward-inverted integrated microscope (San Diego, CA) with a magnification of 100×.…”

Section: Materials and Methodsmentioning

confidence: 99%

Dual Action of Reduced Allergenicity and Improved Memory of Instant Soybean Powder Hydrolysates

Ding,

Huang,

Yang

et al. 2023

J. Agric. Food Chem.

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“…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.…”

Section: Preclinical Studies Of Fluoride and Offspring Growth And Neu...mentioning

confidence: 99%

“… Li et al. [ 123 ] Animal (mice) model N/A Pregnant rats exposed to 100 mg/L of fluoride from gestational day 1–20 with outcomes measured in the male offspring. Gestational day 1 to gestational day 20 Impaired learning and memory.…”

Section: Fluoride From Drinking Water and Childhood Intelligencementioning

confidence: 99%