Dépouillements

Treatment effects of stimulant medication in young boys with fragile X syndrome / J. E. ROBERTS in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.175-84 Titre : Treatment effects of stimulant medication in young boys with fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. E. ROBERTS, Auteur ; M. MIRANDA, Auteur ; M. BOCCIA, Auteur ; H. JANES, Auteur ; B. L. TONNSEN, Auteur ; D. D. HATTON, Auteur Article en page(s) : p.175-84 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is caused by a CGG repeat expansion at Xq27.3 on the FMR1 gene. The majority of young boys with FXS display poor attention and hyperactivity that is disproportionate to their cognitive disability, and approximately 70% meet diagnostic criteria for attention-deficit/hyperactivity disorder. Psychopharmacology is employed with 82% of young males 5-17 years of age, with stimulant medication as the most common medication prescribed. This study evaluated the effects of stimulant medication on the academic performance, attention, motor activity, and psychophysiological arousal of boys with FXS, as well as the concordance of effects within individuals. Participants in this study included 12 boys with FXS who were treated with stimulants. Participants completed videotaped academic testing on two consecutive days and were randomly assigned to be off stimulants for 1 day and on stimulants the other day. On each day, multiple measures including academic performance, behavior regulation, and psychophysiological arousal were collected. Approximately 75% of participants performed better on attention and academic measures, and 70% showed improved physiological regulation while on stimulant medication. A high degree of concordance among measures was found. Lower intelligence quotient (IQ), but not age, correlated with greater improvements in in-seat behavior. IQ and age did not relate to on-task behaviors. The frequency and magnitude of response to stimulant medication in boys with FXS is higher than those reported for most children with non-specific intellectual disabilities and autism spectrum disorder. En ligne : http://dx.doi.org/10.1007/s11689-011-9085-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Treatment effects of stimulant medication in young boys with fragile X syndrome [Texte imprimé et/ou numérique] / J. E. ROBERTS, Auteur ; M. MIRANDA, Auteur ; M. BOCCIA, Auteur ; H. JANES, Auteur ; B. L. TONNSEN, Auteur ; D. D. HATTON, Auteur . - p.175-84. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.175-84 Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and is caused by a CGG repeat expansion at Xq27.3 on the FMR1 gene. The majority of young boys with FXS display poor attention and hyperactivity that is disproportionate to their cognitive disability, and approximately 70% meet diagnostic criteria for attention-deficit/hyperactivity disorder. Psychopharmacology is employed with 82% of young males 5-17 years of age, with stimulant medication as the most common medication prescribed. This study evaluated the effects of stimulant medication on the academic performance, attention, motor activity, and psychophysiological arousal of boys with FXS, as well as the concordance of effects within individuals. Participants in this study included 12 boys with FXS who were treated with stimulants. Participants completed videotaped academic testing on two consecutive days and were randomly assigned to be off stimulants for 1 day and on stimulants the other day. On each day, multiple measures including academic performance, behavior regulation, and psychophysiological arousal were collected. Approximately 75% of participants performed better on attention and academic measures, and 70% showed improved physiological regulation while on stimulant medication. A high degree of concordance among measures was found. Lower intelligence quotient (IQ), but not age, correlated with greater improvements in in-seat behavior. IQ and age did not relate to on-task behaviors. The frequency and magnitude of response to stimulant medication in boys with FXS is higher than those reported for most children with non-specific intellectual disabilities and autism spectrum disorder. En ligne : http://dx.doi.org/10.1007/s11689-011-9085-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

Language and sociability: insights from Williams syndrome / I. FISHMAN in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.185-92 Titre : Language and sociability: insights from Williams syndrome Type de document : Texte imprimé et/ou numérique Auteurs : I. FISHMAN, Auteur ; A. YAM, Auteur ; Ursula BELLUGI, Auteur ; D. MILLS, Auteur Article en page(s) : p.185-92 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : One of the most compelling features of Williams syndrome (WS) is the widely reported excessive sociability, accompanied by a relative proficiency in expressive language, which stands in stark contrast with significant intellectual and nonverbal impairments. It has been proposed that the unique language skills observed in WS are implicated in the strong drive to interact and communicate with others, which has been widely documented in WS. Nevertheless, this proposition has yet to be empirically examined. The present study aimed at investigating the relationship between a brain index of language processing and judgments of approachability of faces, as a proxy for sociability, in individuals with WS as contrasted to typical controls. Results revealed a significant and substantial association between the two in the WS, but not in the control group, supporting the hitherto untested notion that language use in WS might be uniquely related to their excessive social drive. En ligne : http://dx.doi.org/10.1007/s11689-011-9086-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Language and sociability: insights from Williams syndrome [Texte imprimé et/ou numérique] / I. FISHMAN, Auteur ; A. YAM, Auteur ; Ursula BELLUGI, Auteur ; D. MILLS, Auteur . - p.185-92. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.185-92 Index. décimale : PER Périodiques Résumé : One of the most compelling features of Williams syndrome (WS) is the widely reported excessive sociability, accompanied by a relative proficiency in expressive language, which stands in stark contrast with significant intellectual and nonverbal impairments. It has been proposed that the unique language skills observed in WS are implicated in the strong drive to interact and communicate with others, which has been widely documented in WS. Nevertheless, this proposition has yet to be empirically examined. The present study aimed at investigating the relationship between a brain index of language processing and judgments of approachability of faces, as a proxy for sociability, in individuals with WS as contrasted to typical controls. Results revealed a significant and substantial association between the two in the WS, but not in the control group, supporting the hitherto untested notion that language use in WS might be uniquely related to their excessive social drive. En ligne : http://dx.doi.org/10.1007/s11689-011-9086-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

Targeted treatments for fragile X syndrome / Elizabeth BERRY-KRAVIS in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.193-210 Titre : Targeted treatments for fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Elizabeth BERRY-KRAVIS, Auteur ; A. KNOX, Auteur ; C. HERVEY, Auteur Article en page(s) : p.193-210 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet full criteria for ASD. Recent major advances have been made in the understanding of the neurobiology and functions of FMRP, the FMR1 (fragile X mental retardation 1) gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to the dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to the dysregulated translational pathway. These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model at multiple stages of development. Clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess cognitive change that might be associated with treatment. Genes known to be causes of ASD interact with the translational pathway defective in FXS, and it has been hypothesized that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction between FXS and ASD. Therefore, targeted treatments developed for FXS may also target subgroups of ASD, and clinical trials in FXS may serve as a model for the development of clinical trial strategies for ASD and other cognitive disorders. En ligne : http://dx.doi.org/10.1007/s11689-011-9074-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Targeted treatments for fragile X syndrome [Texte imprimé et/ou numérique] / Elizabeth BERRY-KRAVIS, Auteur ; A. KNOX, Auteur ; C. HERVEY, Auteur . - p.193-210. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.193-210 Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet full criteria for ASD. Recent major advances have been made in the understanding of the neurobiology and functions of FMRP, the FMR1 (fragile X mental retardation 1) gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to the dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to the dysregulated translational pathway. These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model at multiple stages of development. Clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess cognitive change that might be associated with treatment. Genes known to be causes of ASD interact with the translational pathway defective in FXS, and it has been hypothesized that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction between FXS and ASD. Therefore, targeted treatments developed for FXS may also target subgroups of ASD, and clinical trials in FXS may serve as a model for the development of clinical trial strategies for ASD and other cognitive disorders. En ligne : http://dx.doi.org/10.1007/s11689-011-9074-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

FMR1 premutation and full mutation molecular mechanisms related to autism / Randi J. HAGERMAN in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.211-24 Titre : FMR1 premutation and full mutation molecular mechanisms related to autism Type de document : Texte imprimé et/ou numérique Auteurs : Randi J. HAGERMAN, Auteur ; J. AU, Auteur ; Paul J. HAGERMAN, Auteur Article en page(s) : p.211-24 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5' un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9084-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] FMR1 premutation and full mutation molecular mechanisms related to autism [Texte imprimé et/ou numérique] / Randi J. HAGERMAN, Auteur ; J. AU, Auteur ; Paul J. HAGERMAN, Auteur . - p.211-24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.211-24 Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5' un-translated portion of the fragile X mental retardation 1 gene (FMR1) leading to a deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA-binding protein that regulates the translation of a number of other genes that are important for synaptic development and plasticity. Furthermore, many of these genes, when mutated, have been linked to autism in the general population, which may explain the high comorbidity that exists between FXS and autism spectrum disorders (ASD). Additionally, premutation repeat expansions (55 to 200 CGG repeats) may also give rise to ASD through a different molecular mechanism that involves a direct toxic effect of FMR1 mRNA. It is believed that RNA toxicity underlies much of the premutation-related involvement, including developmental concerns like autism, as well as neurodegenerative issues with aging such as the fragile X-associated tremor ataxia syndrome (FXTAS). RNA toxicity can also lead to mitochondrial dysfunction, which is common in older premutation carriers both with and without FXTAS. Many of the problems with cellular dysregulation in both premutation and full mutation neurons also parallel the cellular abnormalities that have been documented in idiopathic autism. Research regarding dysregulation of neurotransmitter systems caused by the lack of FMRP in FXS, including metabotropic glutamate receptor 1/5 (mGluR1/5) pathway and GABA pathways, has led to new targeted treatments for FXS. Preliminary evidence suggests that these new targeted treatments will also be beneficial in non-fragile X forms of autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9084-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

Prader-Willi syndrome and autism spectrum disorders: an evolving story / E. M. DYKENS in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.225-37 Titre : Prader-Willi syndrome and autism spectrum disorders: an evolving story Type de document : Texte imprimé et/ou numérique Auteurs : E. M. DYKENS, Auteur ; E. LEE, Auteur ; E. ROOF, Auteur Article en page(s) : p.225-37 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Prader-Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11-q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11-q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9092-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Prader-Willi syndrome and autism spectrum disorders: an evolving story [Texte imprimé et/ou numérique] / E. M. DYKENS, Auteur ; E. LEE, Auteur ; E. ROOF, Auteur . - p.225-37. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.225-37 Index. décimale : PER Périodiques Résumé : Prader-Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11-q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11-q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9092-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

DNA methylation, the early-life social environment and behavioral disorders / M. SZYF in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.238-49 Titre : DNA methylation, the early-life social environment and behavioral disorders Type de document : Texte imprimé et/ou numérique Auteurs : M. SZYF, Auteur Article en page(s) : p.238-49 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : One of the outstanding questions in behavioral disorders is untangling the complex relationship between nurture and nature. Although epidemiological data provide evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in a spectrum of behavioral disorders, the main open question remains the mechanism. Emerging data support the hypothesis that DNA methylation, a covalent modification of the DNA molecule that is a component of its chemical structure, serves as an interface between the dynamic environment and the fixed genome. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome adaptation. Under certain contexts, this adaptation can turn maladaptive resulting in behavioral disorders. This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed. En ligne : http://dx.doi.org/10.1007/s11689-011-9079-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] DNA methylation, the early-life social environment and behavioral disorders [Texte imprimé et/ou numérique] / M. SZYF, Auteur . - p.238-49. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.238-49 Index. décimale : PER Périodiques Résumé : One of the outstanding questions in behavioral disorders is untangling the complex relationship between nurture and nature. Although epidemiological data provide evidence that there is an interaction between genetics (nature) and the social and physical environments (nurture) in a spectrum of behavioral disorders, the main open question remains the mechanism. Emerging data support the hypothesis that DNA methylation, a covalent modification of the DNA molecule that is a component of its chemical structure, serves as an interface between the dynamic environment and the fixed genome. We propose that modulation of DNA methylation in response to environmental cues early in life serves as a mechanism of life-long genome adaptation. Under certain contexts, this adaptation can turn maladaptive resulting in behavioral disorders. This hypothesis has important implications on understanding, predicting, preventing, and treating behavioral disorders including autism that will be discussed. En ligne : http://dx.doi.org/10.1007/s11689-011-9079-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

Role of MeCP2, DNA methylation, and HDACs in regulating synapse function / E. T. KAVALALI in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.250-6 Titre : Role of MeCP2, DNA methylation, and HDACs in regulating synapse function Type de document : Texte imprimé et/ou numérique Auteurs : E. T. KAVALALI, Auteur ; E. D. NELSON, Auteur ; L. M. MONTEGGIA, Auteur Article en page(s) : p.250-6 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Over the past several years there has been intense effort to delineate the role of epigenetic factors, including methyl-CpG-binding protein 2, histone deacetylases, and DNA methyltransferases, in synaptic function. Studies from our group as well as others have shown that these key epigenetic mechanisms are critical regulators of synapse formation, maturation, as well as function. Although most studies have identified selective deficits in excitatory neurotransmission, the latest work has also uncovered deficits in inhibitory neurotransmission as well. Despite the rapid pace of advances, the exact synaptic mechanisms and gene targets that mediate these effects on neurotransmission remain unclear. Nevertheless, these findings not only open new avenues for understanding neuronal circuit abnormalities associated with neurodevelopmental disorders but also elucidate potential targets for addressing the pathophysiology of several intractable neuropsychiatric disorders. En ligne : http://dx.doi.org/10.1007/s11689-011-9078-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Role of MeCP2, DNA methylation, and HDACs in regulating synapse function [Texte imprimé et/ou numérique] / E. T. KAVALALI, Auteur ; E. D. NELSON, Auteur ; L. M. MONTEGGIA, Auteur . - p.250-6. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.250-6 Index. décimale : PER Périodiques Résumé : Over the past several years there has been intense effort to delineate the role of epigenetic factors, including methyl-CpG-binding protein 2, histone deacetylases, and DNA methyltransferases, in synaptic function. Studies from our group as well as others have shown that these key epigenetic mechanisms are critical regulators of synapse formation, maturation, as well as function. Although most studies have identified selective deficits in excitatory neurotransmission, the latest work has also uncovered deficits in inhibitory neurotransmission as well. Despite the rapid pace of advances, the exact synaptic mechanisms and gene targets that mediate these effects on neurotransmission remain unclear. Nevertheless, these findings not only open new avenues for understanding neuronal circuit abnormalities associated with neurodevelopmental disorders but also elucidate potential targets for addressing the pathophysiology of several intractable neuropsychiatric disorders. En ligne : http://dx.doi.org/10.1007/s11689-011-9078-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders / S. DE RUBEIS in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.257-69 Titre : Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : S. DE RUBEIS, Auteur ; C. BAGNI, Auteur Article en page(s) : p.257-69 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The Fragile X syndrome (FXS) is a leading cause of intellectual disability (ID) and autism. The disease is caused by mutations or loss of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein playing multiple functions in RNA metabolism. The expression of a large set of neuronal mRNAs is altered when FMRP is lost, thus causing defects in neuronal morphology and physiology. FMRP regulates mRNA stability, dendritic targeting, and protein synthesis. At synapses, FMRP represses protein synthesis by forming a complex with the Cytoplasmic FMRP Interacting Protein 1 (CYFIP1) and the cap-binding protein eIF4E. Here, we review the clinical, genetic, and molecular aspects of FXS with a special focus on the receptor signaling that regulates FMRP-dependent protein synthesis. We further discuss the FMRP-CYFIP1 complex and its potential relevance for ID and autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9087-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders [Texte imprimé et/ou numérique] / S. DE RUBEIS, Auteur ; C. BAGNI, Auteur . - p.257-69. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.257-69 Index. décimale : PER Périodiques Résumé : The Fragile X syndrome (FXS) is a leading cause of intellectual disability (ID) and autism. The disease is caused by mutations or loss of the Fragile X Mental Retardation Protein (FMRP), an RNA-binding protein playing multiple functions in RNA metabolism. The expression of a large set of neuronal mRNAs is altered when FMRP is lost, thus causing defects in neuronal morphology and physiology. FMRP regulates mRNA stability, dendritic targeting, and protein synthesis. At synapses, FMRP represses protein synthesis by forming a complex with the Cytoplasmic FMRP Interacting Protein 1 (CYFIP1) and the cap-binding protein eIF4E. Here, we review the clinical, genetic, and molecular aspects of FXS with a special focus on the receptor signaling that regulates FMRP-dependent protein synthesis. We further discuss the FMRP-CYFIP1 complex and its potential relevance for ID and autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9087-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

The neurobiology of mouse models syntenic to human chromosome 15q / T. TAKUMI in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.270-81 Titre : The neurobiology of mouse models syntenic to human chromosome 15q Type de document : Texte imprimé et/ou numérique Auteurs : T. TAKUMI, Auteur Article en page(s) : p.270-81 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism is a neurodevelopmental disorder that manifests in childhood as social behavioral abnormalities, such as abnormal social interaction, impaired communication, and restricted interest or behavior. Of the known causes of autism, duplication of human chromosome 15q11-q13 is the most frequently associated cytogenetic abnormality. Chromosome 15q11-q13 is also known to include imprinting genes. In terms of neuroscience, it contains interesting genes such as Necdin, Ube3a, and a cluster of GABA(A) subunits as well as huge clusters of non-coding RNAs (small nucleolar RNAs, snoRNAs). Phenotypic analyses of mice genetically or chromosomally engineered for each gene or their clusters on a region of mouse chromosome seven syntenic to human 15q11-q13 indicate that this region may be involved in social behavior, serotonin metabolism, and weight control. Further studies using these models will provide important clues to the pathophysiology of autism. This review overviews phenotypes of mouse models of genes in 15q11-q13 and their relationships to autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9088-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] The neurobiology of mouse models syntenic to human chromosome 15q [Texte imprimé et/ou numérique] / T. TAKUMI, Auteur . - p.270-81. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.270-81 Index. décimale : PER Périodiques Résumé : Autism is a neurodevelopmental disorder that manifests in childhood as social behavioral abnormalities, such as abnormal social interaction, impaired communication, and restricted interest or behavior. Of the known causes of autism, duplication of human chromosome 15q11-q13 is the most frequently associated cytogenetic abnormality. Chromosome 15q11-q13 is also known to include imprinting genes. In terms of neuroscience, it contains interesting genes such as Necdin, Ube3a, and a cluster of GABA(A) subunits as well as huge clusters of non-coding RNAs (small nucleolar RNAs, snoRNAs). Phenotypic analyses of mice genetically or chromosomally engineered for each gene or their clusters on a region of mouse chromosome seven syntenic to human 15q11-q13 indicate that this region may be involved in social behavior, serotonin metabolism, and weight control. Further studies using these models will provide important clues to the pathophysiology of autism. This review overviews phenotypes of mouse models of genes in 15q11-q13 and their relationships to autism. En ligne : http://dx.doi.org/10.1007/s11689-011-9088-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

A new synaptic player leading to autism risk: Met receptor tyrosine kinase / M. C. JUDSON in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.282-92 Titre : A new synaptic player leading to autism risk: Met receptor tyrosine kinase Type de document : Texte imprimé et/ou numérique Auteurs : M. C. JUDSON, Auteur ; K. L. EAGLESON, Auteur ; P. LEVITT, Auteur Article en page(s) : p.282-92 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET expression in the human cortex. The timing of Met expression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD. En ligne : http://dx.doi.org/10.1007/s11689-011-9081-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] A new synaptic player leading to autism risk: Met receptor tyrosine kinase [Texte imprimé et/ou numérique] / M. C. JUDSON, Auteur ; K. L. EAGLESON, Auteur ; P. LEVITT, Auteur . - p.282-92. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-3 (September 2011) . - p.282-92 Index. décimale : PER Périodiques Résumé : The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET expression in the human cortex. The timing of Met expression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD. En ligne : http://dx.doi.org/10.1007/s11689-011-9081-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343