A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood / E. DE WATER in Journal of Child Psychology and Psychiatry, 60-9 (September 2019)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 60-9 (September 2019) . - p.1010-1020 Titre : A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood Type de document : Texte imprimé et/ou numérique Auteurs : E. DE WATER, Auteur ; P. CURTIN, Auteur ; A. ZILVERSTAND, Auteur ; A. SJODIN, Auteur ; A. BONILLA, Auteur ; J. B. HERBSTMAN, Auteur ; J. RAMIREZ, Auteur ; A. E. MARGOLIS, Auteur ; R. BANSAL, Auteur ; R. M. WHYATT, Auteur ; B. S. PETERSON, Auteur ; P. FACTOR-LITVAK, Auteur ; M. K. HORTON, Auteur Article en page(s) : p.1010-1020 Langues : Anglais (eng) Mots-clés : Children  executive functioning  flame retardants  pregnancy  resting state fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood. METHODS: In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph-theoretical approach) in 5-year-old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems. RESULTS: Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (beta's = .01, FDR-corrected p's En ligne : http://dx.doi.org/10.1111/jcpp.13040 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405 [article] A preliminary study on prenatal polybrominated diphenyl ether serum concentrations and intrinsic functional network organization and executive functioning in childhood [Texte imprimé et/ou numérique] / E. DE WATER, Auteur ; P. CURTIN, Auteur ; A. ZILVERSTAND, Auteur ; A. SJODIN, Auteur ; A. BONILLA, Auteur ; J. B. HERBSTMAN, Auteur ; J. RAMIREZ, Auteur ; A. E. MARGOLIS, Auteur ; R. BANSAL, Auteur ; R. M. WHYATT, Auteur ; B. S. PETERSON, Auteur ; P. FACTOR-LITVAK, Auteur ; M. K. HORTON, Auteur . - p.1010-1020. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 60-9 (September 2019) . - p.1010-1020 Mots-clés : Children  executive functioning  flame retardants  pregnancy  resting state fMRI Index. décimale : PER Périodiques Résumé : BACKGROUND: The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood. METHODS: In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph-theoretical approach) in 5-year-old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent-report questionnaire (BRIEF-P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems. RESULTS: Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (beta's = .01, FDR-corrected p's En ligne : http://dx.doi.org/10.1111/jcpp.13040 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=405

Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons / N. URRACA in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 6p. Titre : Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons Type de document : Texte imprimé et/ou numérique Auteurs : N. URRACA, Auteur ; K. HOPE, Auteur ; A. K. VICTOR, Auteur ; T. G. BELGARD, Auteur ; R. MEMON, Auteur ; S. GOORHA, Auteur ; C. VALDEZ, Auteur ; Q. T. TRAN, Auteur ; S. SANCHEZ, Auteur ; J. RAMIREZ, Auteur ; M. DONALDSON, Auteur ; D. BRIDGES, Auteur ; L. T. REITER, Auteur Article en page(s) : 6p. Langues : Anglais (eng) Mots-clés : Autism  Genomic disorders  Neurogenetic syndrome  Stem cells  mRNAseq Index. décimale : PER Périodiques Résumé : Background: The inability to analyze gene expression in living neurons from Angelman (AS) and Duplication 15q (Dup15q) syndrome subjects has limited our understanding of these disorders at the molecular level. Method: Here, we use dental pulp stem cells (DPSC) from AS deletion, 15q Duplication, and neurotypical control subjects for whole transcriptome analysis. We identified 20 genes unique to AS neurons, 120 genes unique to 15q duplication, and 3 shared transcripts that were differentially expressed in DPSC neurons vs controls. Results: Copy number correlated with gene expression for most genes across the 15q11.2-q13.1 critical region. Two thirds of the genes differentially expressed in 15q duplication neurons were downregulated compared to controls including several transcription factors, while in AS differential expression was restricted primarily to the 15q region. Here, we show significant downregulation of the transcription factors FOXO1 and HAND2 in neurons from 15q duplication, but not AS deletion subjects suggesting that disruptions in transcriptional regulation may be a driving factor in the autism phenotype in Dup15q syndrome. Downstream analysis revealed downregulation of the ASD associated genes EHPB2 and RORA, both genes with FOXO1 binding sites. Genes upregulated in either Dup15q cortex or idiopathic ASD cortex both overlapped significantly with the most upregulated genes in Dup15q DPSC-derived neurons. Conclusions: Finding a significant increase in both HERC2 and UBE3A in Dup15q neurons and significant decrease in these two genes in AS deletion neurons may explain differences between AS deletion class and UBE3A specific classes of AS mutation where HERC2 is expressed at normal levels. Also, we identified an enrichment for FOXO1-regulated transcripts in Dup15q neurons including ASD-associated genes EHPB2 and RORA indicating a possible connection between this syndromic form of ASD and idiopathic cases. En ligne : http://dx.doi.org/10.1186/s13229-018-0191-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] Significant transcriptional changes in 15q duplication but not Angelman syndrome deletion stem cell-derived neurons [Texte imprimé et/ou numérique] / N. URRACA, Auteur ; K. HOPE, Auteur ; A. K. VICTOR, Auteur ; T. G. BELGARD, Auteur ; R. MEMON, Auteur ; S. GOORHA, Auteur ; C. VALDEZ, Auteur ; Q. T. TRAN, Auteur ; S. SANCHEZ, Auteur ; J. RAMIREZ, Auteur ; M. DONALDSON, Auteur ; D. BRIDGES, Auteur ; L. T. REITER, Auteur . - 6p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 6p. Mots-clés : Autism  Genomic disorders  Neurogenetic syndrome  Stem cells  mRNAseq Index. décimale : PER Périodiques Résumé : Background: The inability to analyze gene expression in living neurons from Angelman (AS) and Duplication 15q (Dup15q) syndrome subjects has limited our understanding of these disorders at the molecular level. Method: Here, we use dental pulp stem cells (DPSC) from AS deletion, 15q Duplication, and neurotypical control subjects for whole transcriptome analysis. We identified 20 genes unique to AS neurons, 120 genes unique to 15q duplication, and 3 shared transcripts that were differentially expressed in DPSC neurons vs controls. Results: Copy number correlated with gene expression for most genes across the 15q11.2-q13.1 critical region. Two thirds of the genes differentially expressed in 15q duplication neurons were downregulated compared to controls including several transcription factors, while in AS differential expression was restricted primarily to the 15q region. Here, we show significant downregulation of the transcription factors FOXO1 and HAND2 in neurons from 15q duplication, but not AS deletion subjects suggesting that disruptions in transcriptional regulation may be a driving factor in the autism phenotype in Dup15q syndrome. Downstream analysis revealed downregulation of the ASD associated genes EHPB2 and RORA, both genes with FOXO1 binding sites. Genes upregulated in either Dup15q cortex or idiopathic ASD cortex both overlapped significantly with the most upregulated genes in Dup15q DPSC-derived neurons. Conclusions: Finding a significant increase in both HERC2 and UBE3A in Dup15q neurons and significant decrease in these two genes in AS deletion neurons may explain differences between AS deletion class and UBE3A specific classes of AS mutation where HERC2 is expressed at normal levels. Also, we identified an enrichment for FOXO1-regulated transcripts in Dup15q neurons including ASD-associated genes EHPB2 and RORA indicating a possible connection between this syndromic form of ASD and idiopathic cases. En ligne : http://dx.doi.org/10.1186/s13229-018-0191-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

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