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Proteomic explorations of autism spectrum disorder / Nicholas SZOKO in Autism Research, 10-9 (September 2017)
[article]
Titre : Proteomic explorations of autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Nicholas SZOKO, Auteur ; Adam J. MCSHANE, Auteur ; Marvin R. NATOWICZ, Auteur Article en page(s) : p.1460-1469 Langues : Anglais (eng) Mots-clés : autism autistic proteomic proteomics mass spectrometry neuroproteomics Index. décimale : PER Périodiques Résumé : Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue. Some studies found dysregulation of aspects of the immune system or of aspects of lipid metabolism, but no consistent findings were noted. Based on the challenges in using proteomics to study autism, we discuss considerations for future studies. Apart from the complex technical considerations implicit in any proteomic analysis, key nontechnical matters include attention to subject and specimen inclusion/exclusion criteria, having adequate sample size to ensure appropriate powering of the study, attention to the state of specimens prior to proteomic analysis, and the use of a replicate set of specimens, when possible. We conclude by discussing some potentially productive uses of proteomics, potentially coupled with other approaches, for future autism research including: (1) proteomic analysis of banked human brain specimens; (2) proteomic analysis of tissues from animal models of autism; and (3) proteomic analysis of induced pluripotent stem cells that are differentiated into various types of brain cells and neural organoids. En ligne : http://dx.doi.org/10.1002/aur.1803 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=320
in Autism Research > 10-9 (September 2017) . - p.1460-1469[article] Proteomic explorations of autism spectrum disorder [Texte imprimé et/ou numérique] / Nicholas SZOKO, Auteur ; Adam J. MCSHANE, Auteur ; Marvin R. NATOWICZ, Auteur . - p.1460-1469.
Langues : Anglais (eng)
in Autism Research > 10-9 (September 2017) . - p.1460-1469
Mots-clés : autism autistic proteomic proteomics mass spectrometry neuroproteomics Index. décimale : PER Périodiques Résumé : Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue. Some studies found dysregulation of aspects of the immune system or of aspects of lipid metabolism, but no consistent findings were noted. Based on the challenges in using proteomics to study autism, we discuss considerations for future studies. Apart from the complex technical considerations implicit in any proteomic analysis, key nontechnical matters include attention to subject and specimen inclusion/exclusion criteria, having adequate sample size to ensure appropriate powering of the study, attention to the state of specimens prior to proteomic analysis, and the use of a replicate set of specimens, when possible. We conclude by discussing some potentially productive uses of proteomics, potentially coupled with other approaches, for future autism research including: (1) proteomic analysis of banked human brain specimens; (2) proteomic analysis of tissues from animal models of autism; and (3) proteomic analysis of induced pluripotent stem cells that are differentiated into various types of brain cells and neural organoids. En ligne : http://dx.doi.org/10.1002/aur.1803 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=320 Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally / C. E. BARRETT in Molecular Autism, 8 (2017)
[article]
Titre : Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally Type de document : Texte imprimé et/ou numérique Auteurs : C. E. BARRETT, Auteur ; T. M. HENNESSEY, Auteur ; K. M. GORDON, Auteur ; S. J. RYAN, Auteur ; M. L. MCNAIR, Auteur ; K. J. RESSLER, Auteur ; D. G. RAINNIE, Auteur Article en page(s) : 42p. Langues : Anglais (eng) Mots-clés : Autism Basolateral amygdala Protein kinase A Proteomics RNA sequencing Social behavior Transcriptomics Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. METHODS: Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. RESULTS: Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. CONCLUSIONS: As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes. En ligne : http://dx.doi.org/10.1186/s13229-017-0160-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329
in Molecular Autism > 8 (2017) . - 42p.[article] Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally [Texte imprimé et/ou numérique] / C. E. BARRETT, Auteur ; T. M. HENNESSEY, Auteur ; K. M. GORDON, Auteur ; S. J. RYAN, Auteur ; M. L. MCNAIR, Auteur ; K. J. RESSLER, Auteur ; D. G. RAINNIE, Auteur . - 42p.
Langues : Anglais (eng)
in Molecular Autism > 8 (2017) . - 42p.
Mots-clés : Autism Basolateral amygdala Protein kinase A Proteomics RNA sequencing Social behavior Transcriptomics Valproic acid Index. décimale : PER Périodiques Résumé : BACKGROUND: The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. METHODS: Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. RESULTS: Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. CONCLUSIONS: As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes. En ligne : http://dx.doi.org/10.1186/s13229-017-0160-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder / Armand G. NGOUNOU WETIE in Autism Research, 8-3 (June 2015)
[article]
Titre : A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Armand G. NGOUNOU WETIE, Auteur ; Kelly L. WORMWOOD, Auteur ; Stefanie RUSSELL, Auteur ; Jeanne P. RYAN, Auteur ; Costel C. DARIE, Auteur ; Alisa G. WOODS, Auteur Article en page(s) : p.338-350 Langues : Anglais (eng) Mots-clés : ASD proteomics biomarker signature early detection diagnosis Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) prevalence is increasing, with current estimates at 1/68–1/50 individuals diagnosed with an ASD. Diagnosis is based on behavioral assessments. Early diagnosis and intervention is known to greatly improve functional outcomes in people with ASD. Diagnosis, treatment monitoring and prognosis of ASD symptoms could be facilitated with biomarkers to complement behavioral assessments. Mass spectrometry (MS) based proteomics may help reveal biomarkers for ASD. In this pilot study, we have analyzed the salivary proteome in individuals with ASD compared to neurotypical control subjects, using MS-based proteomics. Our goal is to optimize methods for salivary proteomic biomarker discovery and to identify initial putative biomarkers in people with ASDs. The salivary proteome is virtually unstudied in ASD, and saliva could provide an easily accessible biomaterial for analysis. Using nano liquid chromatography-tandem mass spectrometry, we found statistically significant differences in several salivary proteins, including elevated prolactin-inducible protein, lactotransferrin, Ig kappa chain C region, Ig gamma-1 chain C region, Ig lambda-2 chain C regions, neutrophil elastase, polymeric immunoglobulin receptor and deleted in malignant brain tumors 1. Our results indicate that this is an effective method for identification of salivary protein biomarkers, support the concept that immune system and gastrointestinal disturbances may be present in individuals with ASDs and point toward the need for larger studies in behaviorally-characterized individuals. En ligne : http://dx.doi.org/10.1002/aur.1450 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=262
in Autism Research > 8-3 (June 2015) . - p.338-350[article] A Pilot Proteomic Analysis of Salivary Biomarkers in Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Armand G. NGOUNOU WETIE, Auteur ; Kelly L. WORMWOOD, Auteur ; Stefanie RUSSELL, Auteur ; Jeanne P. RYAN, Auteur ; Costel C. DARIE, Auteur ; Alisa G. WOODS, Auteur . - p.338-350.
Langues : Anglais (eng)
in Autism Research > 8-3 (June 2015) . - p.338-350
Mots-clés : ASD proteomics biomarker signature early detection diagnosis Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) prevalence is increasing, with current estimates at 1/68–1/50 individuals diagnosed with an ASD. Diagnosis is based on behavioral assessments. Early diagnosis and intervention is known to greatly improve functional outcomes in people with ASD. Diagnosis, treatment monitoring and prognosis of ASD symptoms could be facilitated with biomarkers to complement behavioral assessments. Mass spectrometry (MS) based proteomics may help reveal biomarkers for ASD. In this pilot study, we have analyzed the salivary proteome in individuals with ASD compared to neurotypical control subjects, using MS-based proteomics. Our goal is to optimize methods for salivary proteomic biomarker discovery and to identify initial putative biomarkers in people with ASDs. The salivary proteome is virtually unstudied in ASD, and saliva could provide an easily accessible biomaterial for analysis. Using nano liquid chromatography-tandem mass spectrometry, we found statistically significant differences in several salivary proteins, including elevated prolactin-inducible protein, lactotransferrin, Ig kappa chain C region, Ig gamma-1 chain C region, Ig lambda-2 chain C regions, neutrophil elastase, polymeric immunoglobulin receptor and deleted in malignant brain tumors 1. Our results indicate that this is an effective method for identification of salivary protein biomarkers, support the concept that immune system and gastrointestinal disturbances may be present in individuals with ASDs and point toward the need for larger studies in behaviorally-characterized individuals. En ligne : http://dx.doi.org/10.1002/aur.1450 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=262
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Titre : Synapse Proteomes and Disease: The MASC Paradigm Type de document : Texte imprimé et/ou numérique Auteurs : Àlex BAYES, Auteur ; Seth G. N. GRANT, Auteur Année de publication : 2016 Importance : p.85-99 Langues : Anglais (eng) Mots-clés : Autism Cognition Intellectual disability Learning MAGUK MASC Proteomics Schizophrenia Synapse Synaptopathy Index. décimale : SCI-D SCI-D - Neurosciences Résumé : The synapse is composed of ?2000 proteins, and mutations and genetic variants in these proteins result in a large number of disorders, collectively known as synaptopathies. A major subset of synapse proteins assemble with membrane-associated guanylate kinase (MAGUK) proteins into multiprotein complexes known as MAGUK-associated signaling complexes (MASCs). In total, 145 MASC genes have been related to 197 nervous system conditions. Cognitive behavioral disorders are prominent among these disorders, especially intellectual disability, autism, and schizophrenia. An extensive body of literature in mice has also demonstrated that mutations in MAGUK proteins result in cognitive impairments. Here we provide a detailed analysis of the genetic basis of MASC diseases. These comprehensive studies of synapse complexes and their roles in disease are a general paradigm linking proteomics, genetics, and molecular machines to brain disease. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00006-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Synapse Proteomes and Disease: The MASC Paradigm [Texte imprimé et/ou numérique] / Àlex BAYES, Auteur ; Seth G. N. GRANT, Auteur . - 2016 . - p.85-99.
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Langues : Anglais (eng)
Mots-clés : Autism Cognition Intellectual disability Learning MAGUK MASC Proteomics Schizophrenia Synapse Synaptopathy Index. décimale : SCI-D SCI-D - Neurosciences Résumé : The synapse is composed of ?2000 proteins, and mutations and genetic variants in these proteins result in a large number of disorders, collectively known as synaptopathies. A major subset of synapse proteins assemble with membrane-associated guanylate kinase (MAGUK) proteins into multiprotein complexes known as MAGUK-associated signaling complexes (MASCs). In total, 145 MASC genes have been related to 197 nervous system conditions. Cognitive behavioral disorders are prominent among these disorders, especially intellectual disability, autism, and schizophrenia. An extensive body of literature in mice has also demonstrated that mutations in MAGUK proteins result in cognitive impairments. Here we provide a detailed analysis of the genetic basis of MASC diseases. These comprehensive studies of synapse complexes and their roles in disease are a general paradigm linking proteomics, genetics, and molecular machines to brain disease. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00006-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Exemplaires
Code-barres Cote Support Localisation Section Disponibilité aucun exemplaire An atlas of genetic correlations between gestational age and common psychiatric disorders / Yao YAO in Autism Research, 15-6 (June 2022)
[article]
Titre : An atlas of genetic correlations between gestational age and common psychiatric disorders Type de document : Texte imprimé et/ou numérique Auteurs : Yao YAO, Auteur ; Chun'e LI, Auteur ; Peilin MENG, Auteur ; Bolun CHENG, Auteur ; Shiqiang CHENG, Auteur ; Li LIU, Auteur ; Xuena YANG, Auteur ; Yumeng JIA, Auteur ; Yan WEN, Auteur ; Feng ZHANG, Auteur Article en page(s) : p.1008-1017 Langues : Anglais (eng) Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics Autism Spectrum Disorder/genetics Depressive Disorder, Major/genetics Female Genetic Predisposition to Disease Genome-Wide Association Study Gestational Age Humans Infant, Newborn Mendelian Randomization Analysis Premature Birth/genetics Proteomics genetic correlation linkage disequilibrium score regression psychiatric disorders Index. décimale : PER Périodiques Résumé : We aim to systematically explore the potential genetic correlations between five major psychiatric disorders and gestational ages. Genome-wide association study (GWAS) summary datasets of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) in discovery were downloaded from the Psychiatric GWAS Consortium (PGC) website. Suggestive (Raw p?0.05) genetic associations in the discovery phrase were further replicated in independent GWASs which downloaded from PGC, the FinnGen study or Integrative Psychiatric Research (iPSYCH) website. GWASs of gestational duration, preterm and post-term birth were derived from previous studies of infants from the Early Growth Genetics (EGG) Consortium, the iPSYCH study, and the Genomic and Proteomic Network for Preterm Birth Research (GPN). We calculated genetic correlations using linkage disequilibrium score (LDSC) regression. Mendelian randomization (MR) analyses were performed to investigate the causal effects. We identified four suggestive genetic correlations between psychiatric disorders and gestational age factors in discovery LDSC and two replicated in a confirmation LDSC: gestational duration and ADHD (r(g) = -0.1405, FDR p = 0.0406), post-term birth and SCZ (r(g) = -0.2003, FDR p = 0.0042). We also observed causal effect of post-term birth on SCZ by MR (P(Weighted median) = 0.037, P(Inverse variance weighted) = 0.007). Our analysis suggested no significant evidence of horizontal pleiotropy and heterogeneity. This study showed the genetic correlation evidences between gestational age phenotypes and psychiatric disorders, providing novel clues for understanding the pathogenic factors of common psychiatric disorders. LAY SUMMARY: Whereas gestational age factors were reported to be associated with psychiatric disorders, the genetic relationship and causality remain to be revealed. The present study reported the first large-scale genetic correlations investigation of the associations between gestational age phenotypes and psychiatric disorders. Results indicate causal relationships between post-term birth and schizophrenia (SCZ), as well as suggestive genetic correlations between gestational duration and attention deficit/hyperactivity disorder (ADHD). This study provided novel clues for understanding the pathogenic factors of common psychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2719 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476
in Autism Research > 15-6 (June 2022) . - p.1008-1017[article] An atlas of genetic correlations between gestational age and common psychiatric disorders [Texte imprimé et/ou numérique] / Yao YAO, Auteur ; Chun'e LI, Auteur ; Peilin MENG, Auteur ; Bolun CHENG, Auteur ; Shiqiang CHENG, Auteur ; Li LIU, Auteur ; Xuena YANG, Auteur ; Yumeng JIA, Auteur ; Yan WEN, Auteur ; Feng ZHANG, Auteur . - p.1008-1017.
Langues : Anglais (eng)
in Autism Research > 15-6 (June 2022) . - p.1008-1017
Mots-clés : Attention Deficit Disorder with Hyperactivity/genetics Autism Spectrum Disorder/genetics Depressive Disorder, Major/genetics Female Genetic Predisposition to Disease Genome-Wide Association Study Gestational Age Humans Infant, Newborn Mendelian Randomization Analysis Premature Birth/genetics Proteomics genetic correlation linkage disequilibrium score regression psychiatric disorders Index. décimale : PER Périodiques Résumé : We aim to systematically explore the potential genetic correlations between five major psychiatric disorders and gestational ages. Genome-wide association study (GWAS) summary datasets of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) in discovery were downloaded from the Psychiatric GWAS Consortium (PGC) website. Suggestive (Raw p?0.05) genetic associations in the discovery phrase were further replicated in independent GWASs which downloaded from PGC, the FinnGen study or Integrative Psychiatric Research (iPSYCH) website. GWASs of gestational duration, preterm and post-term birth were derived from previous studies of infants from the Early Growth Genetics (EGG) Consortium, the iPSYCH study, and the Genomic and Proteomic Network for Preterm Birth Research (GPN). We calculated genetic correlations using linkage disequilibrium score (LDSC) regression. Mendelian randomization (MR) analyses were performed to investigate the causal effects. We identified four suggestive genetic correlations between psychiatric disorders and gestational age factors in discovery LDSC and two replicated in a confirmation LDSC: gestational duration and ADHD (r(g) = -0.1405, FDR p = 0.0406), post-term birth and SCZ (r(g) = -0.2003, FDR p = 0.0042). We also observed causal effect of post-term birth on SCZ by MR (P(Weighted median) = 0.037, P(Inverse variance weighted) = 0.007). Our analysis suggested no significant evidence of horizontal pleiotropy and heterogeneity. This study showed the genetic correlation evidences between gestational age phenotypes and psychiatric disorders, providing novel clues for understanding the pathogenic factors of common psychiatric disorders. LAY SUMMARY: Whereas gestational age factors were reported to be associated with psychiatric disorders, the genetic relationship and causality remain to be revealed. The present study reported the first large-scale genetic correlations investigation of the associations between gestational age phenotypes and psychiatric disorders. Results indicate causal relationships between post-term birth and schizophrenia (SCZ), as well as suggestive genetic correlations between gestational duration and attention deficit/hyperactivity disorder (ADHD). This study provided novel clues for understanding the pathogenic factors of common psychiatric disorders. En ligne : http://dx.doi.org/10.1002/aur.2719 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 A brain proteomic investigation of rapamycin effects in the Tsc1(+/-) mouse model / H. WESSELING in Molecular Autism, 8 (2017)
PermalinkEnvironmental Influences on Biochemistry in Autism Spectrum Disorder / Kelly L. WORMWOOD in Autism - Open Access, 4-3 ([01/06/2014])
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