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Auteur X. HUANG |
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Resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation / W. XIE in Molecular Autism, 9 (2018)
[article]
Titre : Resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation Type de document : Texte imprimé et/ou numérique Auteurs : W. XIE, Auteur ; X. GE, Auteur ; L. LI, Auteur ; A. YAO, Auteur ; X. WANG, Auteur ; M. LI, Auteur ; X. GONG, Auteur ; Z. CHU, Auteur ; Z. LU, Auteur ; X. HUANG, Auteur ; Y. JIAO, Auteur ; Y. WANG, Auteur ; M. XIAO, Auteur ; H. CHEN, Auteur ; W. XIANG, Auteur ; P. YAO, Auteur Article en page(s) : 43p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Estrogen receptor beta Lipid metabolism Mitochondria Oxidative stress Progestin Resveratrol Index. décimale : PER Périodiques Résumé : Background: Recent literatures indicate that maternal hormone exposure is a risk factor for autism spectrum disorder (ASD). We hypothesize that prenatal progestin exposure may counteract the neuroprotective effect of estrogen and contribute to ASD development, and we aim to develop a method to ameliorate prenatal progestin exposure-induced autism-like behavior. Methods: Experiment 1: Prenatal progestin exposure-induced offspring are treated with resveratrol (RSV) through either prenatal or postnatal exposure and then used for autism-like behavior testing and other biomedical analyses. Experiment 2: Prenatal norethindrone (NET) exposure-induced offspring are treated with ERbeta knockdown lentivirus together with RSV for further testing. Experiment 3: Pregnant dams are treated with prenatal NET exposure together with RSV, and the offspring are used for further testing. Results: Eight kinds of clinically relevant progestins were used for prenatal exposure in pregnant dams, and the offspring showed decreased ERbeta expression in the amygdala with autism-like behavior. Oral administration of either postnatal or prenatal RSV treatment significantly reversed this effect with ERbeta activation and ameliorated autism-like behavior. Further investigation showed that RSV activates ERbeta and its target genes by demethylation of DNA and histone on the ERbeta promoter, and then minimizes progestin-induced oxidative stress as well as the dysfunction of mitochondria and lipid metabolism in the brain, subsequently ameliorating autism-like behavior. Conclusions: We conclude that resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation. Our data suggest that prenatal progestin exposure is a strong risk factor for autism-like behavior. Many potential clinical progestin applications, including oral contraceptive pills, preterm birth drugs, and progestin-contaminated drinking water or seafood, may be risk factors for ASD. In addition, RSV may be a good candidate for clinically rescuing or preventing ASD symptoms in humans, while high doses of resveratrol used in the animals may be a potential limitation for human application. En ligne : https://dx.doi.org/10.1186/s13229-018-0225-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 43p.[article] Resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation [Texte imprimé et/ou numérique] / W. XIE, Auteur ; X. GE, Auteur ; L. LI, Auteur ; A. YAO, Auteur ; X. WANG, Auteur ; M. LI, Auteur ; X. GONG, Auteur ; Z. CHU, Auteur ; Z. LU, Auteur ; X. HUANG, Auteur ; Y. JIAO, Auteur ; Y. WANG, Auteur ; M. XIAO, Auteur ; H. CHEN, Auteur ; W. XIANG, Auteur ; P. YAO, Auteur . - 43p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 43p.
Mots-clés : Autism spectrum disorder Estrogen receptor beta Lipid metabolism Mitochondria Oxidative stress Progestin Resveratrol Index. décimale : PER Périodiques Résumé : Background: Recent literatures indicate that maternal hormone exposure is a risk factor for autism spectrum disorder (ASD). We hypothesize that prenatal progestin exposure may counteract the neuroprotective effect of estrogen and contribute to ASD development, and we aim to develop a method to ameliorate prenatal progestin exposure-induced autism-like behavior. Methods: Experiment 1: Prenatal progestin exposure-induced offspring are treated with resveratrol (RSV) through either prenatal or postnatal exposure and then used for autism-like behavior testing and other biomedical analyses. Experiment 2: Prenatal norethindrone (NET) exposure-induced offspring are treated with ERbeta knockdown lentivirus together with RSV for further testing. Experiment 3: Pregnant dams are treated with prenatal NET exposure together with RSV, and the offspring are used for further testing. Results: Eight kinds of clinically relevant progestins were used for prenatal exposure in pregnant dams, and the offspring showed decreased ERbeta expression in the amygdala with autism-like behavior. Oral administration of either postnatal or prenatal RSV treatment significantly reversed this effect with ERbeta activation and ameliorated autism-like behavior. Further investigation showed that RSV activates ERbeta and its target genes by demethylation of DNA and histone on the ERbeta promoter, and then minimizes progestin-induced oxidative stress as well as the dysfunction of mitochondria and lipid metabolism in the brain, subsequently ameliorating autism-like behavior. Conclusions: We conclude that resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation. Our data suggest that prenatal progestin exposure is a strong risk factor for autism-like behavior. Many potential clinical progestin applications, including oral contraceptive pills, preterm birth drugs, and progestin-contaminated drinking water or seafood, may be risk factors for ASD. In addition, RSV may be a good candidate for clinically rescuing or preventing ASD symptoms in humans, while high doses of resveratrol used in the animals may be a potential limitation for human application. En ligne : https://dx.doi.org/10.1186/s13229-018-0225-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371