Maternal exposure to triclosan constitutes a yet unrecognized risk factor for autism spectrum disorders

Hao, Zijian; Wu, Qionghui; Li, Yali; Li, Qiu; Lai, Xi; Huan, Liu; Zhang, Menghuan; Yang, Ting; Chen, Jie; Tang, Yaping; Miao, Jing-Kun; Xu, Huatai; Li, Tingyu; Hu, Ronggui

doi:10.1038/s41422-019-0220-1

Cited by 29 publications

(10 citation statements)

References 15 publications

(15 reference statements)

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“…Metformin, a widely-used anti-diabetic drug, was found to rescue the social novelty deficit, repetitive behaviors, and abnormal incidence of seizures in Fmr1 KO mice through normalizing ERK signaling (Gantois et al, 2017). Recently, increasing amount of evidence has suggested an association between impaired RA signaling and ASD (Pavăl et al, 2017;Chen et al, 2018;Zhou and Li, 2018;Hao et al, 2019). Furthermore, the perturbation of synaptic plasticity homeostasis mediated by RA was observed in Fmr1 KO mice and FXS patient-derived induced pluripotent stem (iPS) cells (Soden and Chen, 2010;Zhang et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

et al. 2022

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Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.

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Section: Discussionmentioning

confidence: 99%

Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

et al. 2022

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“…VA has been shown to be critical for cognitive development and normal neurological function of ASD patients. Several studies have reported VAD-related genetic and molecular abnormalities associated with children with ASD, including reduced serum levels of RA ( 26 , 27 ), beta-carotene ( 28 ), and RALDH1 ( 29 ). We previously found that among children with ASD suffering from multivitamin deficiency, the VAD rate was the highest, at up to 77.9% ( 30 ) in Chongqing, China.…”

Section: Discussionmentioning

confidence: 99%

Vitamin A Status Is More Commonly Associated With Symptoms and Neurodevelopment in Boys With Autism Spectrum Disorders—A Multicenter Study in China

et al. 2022

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BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder, and show a striking male bias in prevalence. Vitamin A (VA) is essential for brain development, and abnormalities in its metabolite retinoic acid are associated with the pathophysiology of ASD. This national multicenter study was conducted to investigate the relationship between serum VA level and core symptoms in ASD children and whether there are still sex differences.MethodA total of 1,300 children with ASD and 1,252 typically-developing (TD) controls aged 2–7 years old from 13 cities in China were enrolled in this study. The symptoms of children with ASD were evaluated by the Autism Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Childhood autism rating scale (CARS). The neurodevelopmental level of the children was evaluated with the revised Children Neuropsychological and Behavior Scale (CNBS-R2016). The serum level of VA was measured by high-performance liquid chromatography (HPLC).ResultsThe serum VA level in children with ASD was significantly lower than that in TD children, especially in boys with ASD. Furthermore, VA levels in male children with ASD were lower than those in female children with ASD. In addition, we found that serum VA level was negatively correlated the SRS, CARS and communication warming behavior of CBNS-R2016 scores in boys with ASD. In terms of developmental quotients, serum VA level was positively associated with the general quotient, language quotient, gross motor quotient and personal-social quotient of boys with ASD, but no difference was found in girls with ASD.ConclusionsASD children, especially boys, have lower serum VA levels than TD children. Moreover, serum VA status is more commonly associated with clinical symptoms and neurodevelopment in boys with ASD.

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“…In wild‐type rats, maternal exposure to triclosan (50 mg/kg/d; dissolved in corn oil) from Day 7.5 of pregnancy (E7.5) until weaning (postnatal Day 21, PND21) disrupted the neuronal retinoic acid (RA) signaling in the offspring brain which was speculated to induce autistic‐like behavior in the offspring. [ 85 ] Pups spent more time in chambers having familiar rats or objects and a comparatively lesser time with the stranger rats. They also spent a longer time in self‐grooming and showed an increased anxiety.…”

Section: Triclosan Induced Neurotoxicitymentioning

confidence: 99%

“…They also spent a longer time in self‐grooming and showed an increased anxiety. These behavioral changes can be attributed to the reduced expression of target genes and mediators of RA signaling, RA receptor alpha and beta in the prefrontal cortex of these offspring induced by triclosan, [ 85 ] since manipulation of RA signaling has been already shown to alter behavior. [ 86 ] Maternal exposure to 10 and 100 mg triclosan/kg in mice resulted in offspring with a reduced brain weight, memory deficits and anxiety.…”

Section: Triclosan Induced Neurotoxicitymentioning

confidence: 99%

Neurotoxic mechanisms of triclosan: The antimicrobial agent emerging as a toxicant

Pullaguri

Umale

Bhargava

2022

J Biochem & Molecular Tox

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Several scientific studies have suggested a link between increased exposure to pollutants and a rise in the number of neurodegenerative disorders of unknown origin. Notably, triclosan (an antimicrobial agent) is used in concentrations ranging from 0.3% to 1% in various consumer products. Recent studies have also highlighted triclosan as an emerging toxic pollutant due to its increasing global use. However, a definitive link is missing to associate the rising use of triclosan and the growing number of neurodegenerative disorders or neurotoxicity. In this article, we present systematic scientific evidence which are otherwise scattered to suggest that triclosan can indeed induce neurotoxic effects, especially in vertebrate organisms including humans. Mechanistically, triclosan affected important developmental and differentiation genes, structural genes, genes for signaling receptors and genes for neurotransmitter controlling enzymes. Triclosan-induced oxidative stress impacting cellular proteins and homeostasis which triggers apoptosis.Though the scientific evidence collated in this article unequivocally indicates that triclosan can cause neurotoxicity, further epidemiological studies may be needed to confirm the effects on humans.

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Maternal exposure to triclosan constitutes a yet unrecognized risk factor for autism spectrum disorders

Cited by 29 publications

References 15 publications

Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

Retinoic Acid Supplementation Rescues the Social Deficits in Fmr1 Knockout Mice

Vitamin A Status Is More Commonly Associated With Symptoms and Neurodevelopment in Boys With Autism Spectrum Disorders—A Multicenter Study in China

Neurotoxic mechanisms of triclosan: The antimicrobial agent emerging as a toxicant

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