Alterations in plasma cytokine levels in chinese children with autism spectrum disorder / C. C. HU in Autism Research, 11-7 (July 2018)  

Public ISBD [article]  inAutism Research > 11-7 (July 2018) . - p.989-999 Titre : Alterations in plasma cytokine levels in chinese children with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : C. C. HU, Auteur ; X. XU, Auteur ; G. L. XIONG, Auteur ; Q. XU, Auteur ; B. R. ZHOU, Auteur ; C. Y. LI, Auteur ; Q. QIN, Auteur ; C. X. LIU, Auteur ; H. P. LI, Auteur ; Y. J. SUN, Auteur ; X. YU, Auteur Article en page(s) : p.989-999 Langues : Anglais (eng) Mots-clés : TGF-beta1  TNF-alpha  cytokine  eotaxin  immune  neuroinflammation Index. décimale : PER Périodiques Résumé : Genetic alterations, together with environmental risk factors during infancy and childhood, contribute significantly to the etiology of autism spectrum disorder (ASD), a heterogeneous neurodevelopmental condition characterized by impairments in social interaction and restricted, repetitive behaviors. Mounting evidence points to a critical contribution of immunological risk factors to the development of ASD. By affecting multiple neurodevelopmental processes, immune system dysfunction could act as a point of convergence between genetics and environmental factors in ASD. Previous studies have shown altered cytokine levels in individuals with ASD, but research in Asian populations are limited. Here, we measured the plasma levels of 11 candidate cytokines in ASD and typically developing (TD) children. The cohort included 41 TD children and 87 children with ASD, aged 1-6 years. We found that as compared to the TD group, children with ASD had higher plasma levels of Eotaxin, TGF-beta1 and TNF-alpha. The increase in TGF-beta1 level was most significant in males, while the increase in Eotaxin was most significant in females. Eotaxin level negatively correlated with the social affect score (SA) in ADOS, while TNF-alpha level positively correlated with total development quotient (DQ), measured using GMDS. These pilot findings suggest potentially important roles of Eotaxin, TGF-beta1 and TNF-alpha in ASD in the Chinese population. Autism Res 2018, 11: 989-999. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Alteration of immune system function is an important risk factor for autism spectrum disorder (ASD). Here we found that the levels of cytokines, including Eotaxin, TGF-beta1 and TNF-alpha, are elevated in Chinese children with ASD, as compared to typically developing children. The change in TGF-beta1 level was most prominent in boys, while that of Eotaxin was more significant in girls. These results provide evidence for changes in cytokine profile in Chinese children with ASD. En ligne : http://dx.doi.org/10.1002/aur.1940 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=366 [article] Alterations in plasma cytokine levels in chinese children with autism spectrum disorder [Texte imprimé et/ou numérique] / C. C. HU, Auteur ; X. XU, Auteur ; G. L. XIONG, Auteur ; Q. XU, Auteur ; B. R. ZHOU, Auteur ; C. Y. LI, Auteur ; Q. QIN, Auteur ; C. X. LIU, Auteur ; H. P. LI, Auteur ; Y. J. SUN, Auteur ; X. YU, Auteur . - p.989-999. Langues : Anglais (eng) in Autism Research > 11-7 (July 2018) . - p.989-999 Mots-clés : TGF-beta1  TNF-alpha  cytokine  eotaxin  immune  neuroinflammation Index. décimale : PER Périodiques Résumé : Genetic alterations, together with environmental risk factors during infancy and childhood, contribute significantly to the etiology of autism spectrum disorder (ASD), a heterogeneous neurodevelopmental condition characterized by impairments in social interaction and restricted, repetitive behaviors. Mounting evidence points to a critical contribution of immunological risk factors to the development of ASD. By affecting multiple neurodevelopmental processes, immune system dysfunction could act as a point of convergence between genetics and environmental factors in ASD. Previous studies have shown altered cytokine levels in individuals with ASD, but research in Asian populations are limited. Here, we measured the plasma levels of 11 candidate cytokines in ASD and typically developing (TD) children. The cohort included 41 TD children and 87 children with ASD, aged 1-6 years. We found that as compared to the TD group, children with ASD had higher plasma levels of Eotaxin, TGF-beta1 and TNF-alpha. The increase in TGF-beta1 level was most significant in males, while the increase in Eotaxin was most significant in females. Eotaxin level negatively correlated with the social affect score (SA) in ADOS, while TNF-alpha level positively correlated with total development quotient (DQ), measured using GMDS. These pilot findings suggest potentially important roles of Eotaxin, TGF-beta1 and TNF-alpha in ASD in the Chinese population. Autism Res 2018, 11: 989-999. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Alteration of immune system function is an important risk factor for autism spectrum disorder (ASD). Here we found that the levels of cytokines, including Eotaxin, TGF-beta1 and TNF-alpha, are elevated in Chinese children with ASD, as compared to typically developing children. The change in TGF-beta1 level was most prominent in boys, while that of Eotaxin was more significant in girls. These results provide evidence for changes in cytokine profile in Chinese children with ASD. En ligne : http://dx.doi.org/10.1002/aur.1940 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=366

Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons / Q. XU in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 65 p. Titre : Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons Type de document : Texte imprimé et/ou numérique Auteurs : Q. XU, Auteur ; Y. Y. LIU, Auteur ; X. WANG, Auteur ; G. H. TAN, Auteur ; H. P. LI, Auteur ; S. W. HULBERT, Auteur ; C. Y. LI, Auteur ; C. C. HU, Auteur ; Z. Q. XIONG, Auteur ; X. XU, Auteur ; Y. H. JIANG, Auteur Article en page(s) : 65 p. Langues : Anglais (eng) Mots-clés : Animals  Autistic Disorder/*genetics/pathology  Cells, Cultured  Cerebral Cortex/cytology/growth & development  DNA-Binding Proteins/*genetics/metabolism  Humans  Mice  Mice, Inbred C57BL  *Neurogenesis  Neurons/cytology/*metabolism/physiology  *Autism spectrum disorder (ASD)  *chd8  *Chromatin remodeling  *Neurite growth  *Neurodevelopment  Animal Care and Use Committee-approved protocols both at Children's Hospital of  Fudan University ethics approval ID: 2015-87 and Duke University. Human  postmortem brain tissues: The use of archived human postmortem brain tissues is  approved by Institute Review Board at Duke University.Not applicableThe authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: Mutations in CHD8, chromodomain helicase DNA-binding protein 8, are among the most replicated and common findings in genetic studies of autism spectrum disorder (ASD). The CHD8 protein is believed to act as a transcriptional regulator by remodeling chromatin structure and recruiting histone H1 to target genes. The mechanism by which deficiency of CHD8 causes ASD has not been fully elucidated. Methods: We examined the expression of CHD8 in human and mouse brains using both immunohistochemistry and RNA in situ hybridization. We performed in utero electroporation, neuronal culture, and biochemical analysis using RNAi to examine the functional consequences of CHD8 deficiency. Results: We discovered that CHD8 is expressed highly in neurons and at low levels in glia cells in both humans and mice. Specifically, CHD8 is localized predominately in the nucleus of both MAP2 and parvalbumin-positive neurons. In the developing mouse brain, expression of Chd8 peaks from E16 to E18 and then decreases significantly at P14 to adulthood. Knockdown of Chd8 results in reduced axon and dendritic growth, disruption of axon projections to the contralateral cortex, and delayed neuronal migration at E18.5 which recovers by P3 and P7. Conclusion: Our findings indicate an important role for CHD8 in dendritic and axon development and neuronal migration and thus offer novel insights to further dissect the underlying molecular and circuit mechanisms of ASD caused by CHD8 deficiency. En ligne : https://dx.doi.org/10.1186/s13229-018-0244-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons [Texte imprimé et/ou numérique] / Q. XU, Auteur ; Y. Y. LIU, Auteur ; X. WANG, Auteur ; G. H. TAN, Auteur ; H. P. LI, Auteur ; S. W. HULBERT, Auteur ; C. Y. LI, Auteur ; C. C. HU, Auteur ; Z. Q. XIONG, Auteur ; X. XU, Auteur ; Y. H. JIANG, Auteur . - 65 p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 65 p. Mots-clés : Animals  Autistic Disorder/*genetics/pathology  Cells, Cultured  Cerebral Cortex/cytology/growth & development  DNA-Binding Proteins/*genetics/metabolism  Humans  Mice  Mice, Inbred C57BL  *Neurogenesis  Neurons/cytology/*metabolism/physiology  *Autism spectrum disorder (ASD)  *chd8  *Chromatin remodeling  *Neurite growth  *Neurodevelopment  Animal Care and Use Committee-approved protocols both at Children's Hospital of  Fudan University ethics approval ID: 2015-87 and Duke University. Human  postmortem brain tissues: The use of archived human postmortem brain tissues is  approved by Institute Review Board at Duke University.Not applicableThe authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: Mutations in CHD8, chromodomain helicase DNA-binding protein 8, are among the most replicated and common findings in genetic studies of autism spectrum disorder (ASD). The CHD8 protein is believed to act as a transcriptional regulator by remodeling chromatin structure and recruiting histone H1 to target genes. The mechanism by which deficiency of CHD8 causes ASD has not been fully elucidated. Methods: We examined the expression of CHD8 in human and mouse brains using both immunohistochemistry and RNA in situ hybridization. We performed in utero electroporation, neuronal culture, and biochemical analysis using RNAi to examine the functional consequences of CHD8 deficiency. Results: We discovered that CHD8 is expressed highly in neurons and at low levels in glia cells in both humans and mice. Specifically, CHD8 is localized predominately in the nucleus of both MAP2 and parvalbumin-positive neurons. In the developing mouse brain, expression of Chd8 peaks from E16 to E18 and then decreases significantly at P14 to adulthood. Knockdown of Chd8 results in reduced axon and dendritic growth, disruption of axon projections to the contralateral cortex, and delayed neuronal migration at E18.5 which recovers by P3 and P7. Conclusion: Our findings indicate an important role for CHD8 in dendritic and axon development and neuronal migration and thus offer novel insights to further dissect the underlying molecular and circuit mechanisms of ASD caused by CHD8 deficiency. En ligne : https://dx.doi.org/10.1186/s13229-018-0244-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

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