Dépouillements

SHANK3 haploinsufficiency: a common but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders / Catalina BETANCUR in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 8 p. Titre : SHANK3 haploinsufficiency: a common but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur Année de publication : 2013 Article en page(s) : 8 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are etiologically heterogeneous, with hundreds of rare, highly penetrant mutations and genomic imbalances involved, each contributing to a very small fraction of cases. As reviewed here, Phelan-McDermid syndrome, caused by deletion of 22q13.33 or SHANK3 mutations, is one of the more prevalent monogenic causes of ASD, explaining at least 0.5% of cases. In this issue of Molecular Autism, Soorya and colleagues evaluated 32 patients with SHANK3 haploinsufficiency using gold-standard diagnostic assessments and showed that 84% met criteria for ASD, including 75% meeting criteria for autism. This study and prior studies demonstrate that this syndrome is also one of the more penetrant causes of ASD. We note that SHANK3 haploinsufficiency remains underdiagnosed, although with the increasingly widespread use of chromosomal microarray analysis and targeted sequencing of SHANK3, the number of cases is bound to rise. En ligne : http://dx.doi.org/10.1186/2040-2392-4-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] SHANK3 haploinsufficiency: a common but underdiagnosed highly penetrant monogenic cause of autism spectrum disorders [Texte imprimé et/ou numérique] / Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur . - 2013 . - 8 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 8 p. Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are etiologically heterogeneous, with hundreds of rare, highly penetrant mutations and genomic imbalances involved, each contributing to a very small fraction of cases. As reviewed here, Phelan-McDermid syndrome, caused by deletion of 22q13.33 or SHANK3 mutations, is one of the more prevalent monogenic causes of ASD, explaining at least 0.5% of cases. In this issue of Molecular Autism, Soorya and colleagues evaluated 32 patients with SHANK3 haploinsufficiency using gold-standard diagnostic assessments and showed that 84% met criteria for ASD, including 75% meeting criteria for autism. This study and prior studies demonstrate that this syndrome is also one of the more penetrant causes of ASD. We note that SHANK3 haploinsufficiency remains underdiagnosed, although with the increasingly widespread use of chromosomal microarray analysis and targeted sequencing of SHANK3, the number of cases is bound to rise. En ligne : http://dx.doi.org/10.1186/2040-2392-4-17 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Decreased tryptophan metabolism in patients with autism spectrum disorders / Luigi BOCCUTO in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 10 p. Titre : Decreased tryptophan metabolism in patients with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Luigi BOCCUTO, Auteur ; Chin-Fu CHEN, Auteur ; Ayla PITTMAN, Auteur ; Cindy SKINNER, Auteur ; Heather MCCARTNEY, Auteur ; Kelly JONES, Auteur ; Barry BOCHNER, Auteur ; Roger STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur Année de publication : 2013 Article en page(s) : 10 p. Langues : Anglais (eng) Mots-clés : Autism  Biomarker  Tryptophan  Metabolism  Screening Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions.METHODS:We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays.RESULTS:Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients.CONCLUSIONS:Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs. En ligne : http://dx.doi.org/10.1186/2040-2392-4-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Decreased tryptophan metabolism in patients with autism spectrum disorders [Texte imprimé et/ou numérique] / Luigi BOCCUTO, Auteur ; Chin-Fu CHEN, Auteur ; Ayla PITTMAN, Auteur ; Cindy SKINNER, Auteur ; Heather MCCARTNEY, Auteur ; Kelly JONES, Auteur ; Barry BOCHNER, Auteur ; Roger STEVENSON, Auteur ; Charles E. SCHWARTZ, Auteur . - 2013 . - 10 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 10 p. Mots-clés : Autism  Biomarker  Tryptophan  Metabolism  Screening Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. Several biochemical markers have been associated with ASDs, but there is still no laboratory test for these conditions.METHODS:We analyzed the metabolic profile of lymphoblastoid cell lines from 137 patients with neurodevelopmental disorders with or without ASDs and 78 normal individuals, using Biolog Phenotype MicroArrays.RESULTS:Metabolic profiling of lymphoblastoid cells revealed that the 87 patients with ASD as a clinical feature, as compared to the 78 controls, exhibited on average reduced generation of NADH when tryptophan was the sole energy source. The results correlated with the behavioral traits associated with either syndromal or non-syndromal autism, independent of the genetic background of the individual. The low level of NADH generation in the presence of tryptophan was not observed in cell lines from non-ASD patients with intellectual disability, schizophrenia or conditions exhibiting several similarities with syndromal autism except for the behavioral traits. Analysis of a previous small gene expression study found abnormal levels for some genes involved in tryptophan metabolic pathways in 10 patients.CONCLUSIONS:Tryptophan is a precursor of important compounds, such as serotonin, quinolinic acid, and kynurenic acid, which are involved in neurodevelopment and synaptogenesis. In addition, quinolinic acid is the structural precursor of NAD+, a critical energy carrier in mitochondria. Also, the serotonin branch of the tryptophan metabolic pathway generates NADH. Lastly, the levels of quinolinic and kynurenic acid are strongly influenced by the activity of the immune system. Therefore, decreased tryptophan metabolism may alter brain development, neuroimmune activity and mitochondrial function. Our finding of decreased tryptophan metabolism appears to provide a unifying biochemical basis for ASDs and perhaps an initial step in the development of a diagnostic assay for ASDs. En ligne : http://dx.doi.org/10.1186/2040-2392-4-16 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency / Latha V. SOORYA in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 35 p. Titre : Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency Type de document : Texte imprimé et/ou numérique Auteurs : Latha V. SOORYA, Auteur ; Alexander KOLEVZON, Auteur ; Jessica ZWEIFACH, Auteur ; Teresa LIM, Auteur ; Yuriy DOBRY, Auteur ; Lily SCHWARTZ, Auteur ; Yitzchak FRANK, Auteur ; A. WANG, Auteur ; Guiqing CAI, Auteur ; Elena PARKHOMENKO, Auteur ; Danielle B. HALPERN, Auteur ; David GRODBERG, Auteur ; Benjamin ANGARITA, Auteur ; Judith WILLNER, Auteur ; Amy YANG, Auteur ; Roberto CANITANO, Auteur ; William CHAPLIN, Auteur ; Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur Année de publication : 2013 Article en page(s) : 35 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:22q13 deletion syndrome, also known as Phelan-McDermid syndrome, is a neurodevelopmental disorder characterized by intellectual disability, hypotonia, delayed or absent speech, and autistic features. SHANK3 has been identified as the critical gene in the neurological and behavioral aspects of this syndrome. The phenotype of SHANK3 deficiency has been described primarily from case studies, with limited evaluation of behavioral and cognitive deficits. The present study used a prospective design and inter-disciplinary clinical evaluations to assess patients with SHANK3 deficiency, with the goal to provide a comprehensive picture of the medical and behavioral profile of the syndrome.METHODS:A serially ascertained sample of patients with SHANK3 deficiency (n = 32) was evaluated by a team of child psychiatrists, neurologists, clinical geneticists, molecular geneticists and psychologists. Patients were evaluated for autism spectrum disorder using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-G.RESULTS:Thirty participants with 22q13.3 deletions ranging in size from 101 kb to 8.45 Mb and two participants with de novo SHANK3 mutations were included. The sample was characterized by high rates of autism spectrum disorder: 27 (84%) met criteria for autism spectrum disorder and 24 (75%) for autistic disorder. Most patients (77%) exhibited severe to profound intellectual disability and only five (19%) used some words spontaneously to communicate. Dysmorphic features, hypotonia, gait disturbance, recurring upper respiratory tract infections, gastroesophageal reflux and seizures were also common. Analysis of genotype-phenotype correlations indicated that larger deletions were associated with increased levels of dysmorphic features, medical comorbidities and social communication impairments related to autism. Analyses of individuals with small deletions or point mutations identified features related to SHANK3 haploinsufficiency, including ASD, seizures and abnormal EEG, hypotonia, sleep disturbances, abnormal brain MRI, gastroesophageal reflux, and certain dysmorphic features.CONCLUSIONS:This study supports findings from previous research on the severity of intellectual, motor, and speech impairments seen in SHANK3 deficiency, and highlights the predominance of autism spectrum disorder in the syndrome. Limitations of existing evaluation tools are discussed, along with the need for natural history studies to inform clinical monitoring and treatment development in SHANK3 deficiency. En ligne : http://dx.doi.org/10.1186/2040-2392-4-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency [Texte imprimé et/ou numérique] / Latha V. SOORYA, Auteur ; Alexander KOLEVZON, Auteur ; Jessica ZWEIFACH, Auteur ; Teresa LIM, Auteur ; Yuriy DOBRY, Auteur ; Lily SCHWARTZ, Auteur ; Yitzchak FRANK, Auteur ; A. WANG, Auteur ; Guiqing CAI, Auteur ; Elena PARKHOMENKO, Auteur ; Danielle B. HALPERN, Auteur ; David GRODBERG, Auteur ; Benjamin ANGARITA, Auteur ; Judith WILLNER, Auteur ; Amy YANG, Auteur ; Roberto CANITANO, Auteur ; William CHAPLIN, Auteur ; Catalina BETANCUR, Auteur ; Joseph D. BUXBAUM, Auteur . - 2013 . - 35 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 35 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:22q13 deletion syndrome, also known as Phelan-McDermid syndrome, is a neurodevelopmental disorder characterized by intellectual disability, hypotonia, delayed or absent speech, and autistic features. SHANK3 has been identified as the critical gene in the neurological and behavioral aspects of this syndrome. The phenotype of SHANK3 deficiency has been described primarily from case studies, with limited evaluation of behavioral and cognitive deficits. The present study used a prospective design and inter-disciplinary clinical evaluations to assess patients with SHANK3 deficiency, with the goal to provide a comprehensive picture of the medical and behavioral profile of the syndrome.METHODS:A serially ascertained sample of patients with SHANK3 deficiency (n = 32) was evaluated by a team of child psychiatrists, neurologists, clinical geneticists, molecular geneticists and psychologists. Patients were evaluated for autism spectrum disorder using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-G.RESULTS:Thirty participants with 22q13.3 deletions ranging in size from 101 kb to 8.45 Mb and two participants with de novo SHANK3 mutations were included. The sample was characterized by high rates of autism spectrum disorder: 27 (84%) met criteria for autism spectrum disorder and 24 (75%) for autistic disorder. Most patients (77%) exhibited severe to profound intellectual disability and only five (19%) used some words spontaneously to communicate. Dysmorphic features, hypotonia, gait disturbance, recurring upper respiratory tract infections, gastroesophageal reflux and seizures were also common. Analysis of genotype-phenotype correlations indicated that larger deletions were associated with increased levels of dysmorphic features, medical comorbidities and social communication impairments related to autism. Analyses of individuals with small deletions or point mutations identified features related to SHANK3 haploinsufficiency, including ASD, seizures and abnormal EEG, hypotonia, sleep disturbances, abnormal brain MRI, gastroesophageal reflux, and certain dysmorphic features.CONCLUSIONS:This study supports findings from previous research on the severity of intellectual, motor, and speech impairments seen in SHANK3 deficiency, and highlights the predominance of autism spectrum disorder in the syndrome. Limitations of existing evaluation tools are discussed, along with the need for natural history studies to inform clinical monitoring and treatment development in SHANK3 deficiency. En ligne : http://dx.doi.org/10.1186/2040-2392-4-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder / Yosuke KAMENO in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 6 p. Titre : Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Yosuke KAMENO, Auteur ; Keiko IWATA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masato MAEKAWA, Auteur ; Masatsugu TSUJII, Auteur ; Toshirou SUGIYAMA, Auteur ; Norio MORI, Auteur Année de publication : 2013 Article en page(s) : 6 p. Langues : Anglais (eng) Mots-clés : Autism  Human serum  Adhesion molecules  Platelet-endothelial adhesion molecule-1  Platelet selectin  Endothelial selectin  Intracellular adhesion molecule-1  Vascular cell adhesion molecule-1 Index. décimale : PER Périodiques Résumé : Background Adhesion molecules, such as platelet-endothelial adhesion molecule-1 (PECAM-1), platelet selectin (P-selectin), endothelial selectin (E-selectin), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are localized on the membranes of activated platelets and leukocytes and on the vascular endothelium. Recently, we measured serum levels of soluble (s) forms of adhesion molecules in adults,18 to 26 years old, with autism spectrum disorder (ASD) and observed low levels of sPECAM-1 and sP-selectin. A subsequent study showed a similar result in children two to four years old with ASD. However, information about school age (five to seventeen years old) ASD subjects is required to determine whether adhesion molecules are also reduced in individuals with ASD in this age range. Findings Twenty-two subjects with high-functioning ASD and 29 healthy age-matched controls were recruited. ELISA was used for sPECAM-1, and a suspension array system was used for sP-selectin, sE-selectin, sICAM-1 and sVCAM-1 measurements. We found that serum levels of sPECAM-1 (U = 91.0, P<0.0001 by Mann–Whitney U test) and sVCAM-1 (U = 168.0, P = 0.0042) were significantly lower in ASD subjects than in controls. Subsequently, we examined the correlations between serum levels of either sPECAM-1 or sVCAM-1 and clinical variables including Autism Diagnostic Interview - Revised subscores and our previous cytokine profile data from the same ASD subjects. However, we did not find any significant correlations between them. Conclusions The present results, taken together with previous results, suggest that sPECAM-1 may play a role in the generation and development of ASD, beginning in childhood and lasting until adulthood. En ligne : http://dx.doi.org/10.1186/2040-2392-4-19 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Serum levels of soluble platelet endothelial cell adhesion molecule-1 and vascular cell adhesion molecule-1 are decreased in subjects with autism spectrum disorder [Texte imprimé et/ou numérique] / Yosuke KAMENO, Auteur ; Keiko IWATA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masato MAEKAWA, Auteur ; Masatsugu TSUJII, Auteur ; Toshirou SUGIYAMA, Auteur ; Norio MORI, Auteur . - 2013 . - 6 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 6 p. Mots-clés : Autism  Human serum  Adhesion molecules  Platelet-endothelial adhesion molecule-1  Platelet selectin  Endothelial selectin  Intracellular adhesion molecule-1  Vascular cell adhesion molecule-1 Index. décimale : PER Périodiques Résumé : Background Adhesion molecules, such as platelet-endothelial adhesion molecule-1 (PECAM-1), platelet selectin (P-selectin), endothelial selectin (E-selectin), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), are localized on the membranes of activated platelets and leukocytes and on the vascular endothelium. Recently, we measured serum levels of soluble (s) forms of adhesion molecules in adults,18 to 26 years old, with autism spectrum disorder (ASD) and observed low levels of sPECAM-1 and sP-selectin. A subsequent study showed a similar result in children two to four years old with ASD. However, information about school age (five to seventeen years old) ASD subjects is required to determine whether adhesion molecules are also reduced in individuals with ASD in this age range. Findings Twenty-two subjects with high-functioning ASD and 29 healthy age-matched controls were recruited. ELISA was used for sPECAM-1, and a suspension array system was used for sP-selectin, sE-selectin, sICAM-1 and sVCAM-1 measurements. We found that serum levels of sPECAM-1 (U = 91.0, P<0.0001 by Mann–Whitney U test) and sVCAM-1 (U = 168.0, P = 0.0042) were significantly lower in ASD subjects than in controls. Subsequently, we examined the correlations between serum levels of either sPECAM-1 or sVCAM-1 and clinical variables including Autism Diagnostic Interview - Revised subscores and our previous cytokine profile data from the same ASD subjects. However, we did not find any significant correlations between them. Conclusions The present results, taken together with previous results, suggest that sPECAM-1 may play a role in the generation and development of ASD, beginning in childhood and lasting until adulthood. En ligne : http://dx.doi.org/10.1186/2040-2392-4-19 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Episodic memory retrieval for story characters in high-functioning autism / Hidetsugu KOMEDA in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 9 p. Titre : Episodic memory retrieval for story characters in high-functioning autism Type de document : Texte imprimé et/ou numérique Auteurs : Hidetsugu KOMEDA, Auteur ; Hirotaka KOSAKA, Auteur ; Daisuke N. SAITO, Auteur ; Keisuke INOHARA, Auteur ; Toshio MUNESUE, Auteur ; Makoto ISHITOBI, Auteur ; Makoto SATO, Auteur ; Hidehiko OKAZAWA, Auteur Année de publication : 2013 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : High-functioning autism  Narrative comprehension  Recognition  Memory retrieval  Similarity Index. décimale : PER Périodiques Résumé : Background The objective of this study was to examine differences in episodic memory retrieval between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals. Previous studies have shown that personality similarities between readers and characters facilitated reading comprehension. Highly extraverted participants read stories featuring extraverted protagonists more easily and judged the outcomes of such stories more rapidly than did less extraverted participants. Similarly, highly neurotic participants judged the outcomes of stories with neurotic protagonists more rapidly than did participants with low levels of neuroticism. However, the impact of the similarity effect on memory retrieval remains unclear. This study tested our ‘similarity hypothesis’, namely that memory retrieval is enhanced when readers with ASD and TD readers read stories featuring protagonists with ASD and with characteristics associated with TD individuals, respectively. Methods Eighteen Japanese individuals (one female) with high-functioning ASD (aged 17 to 40 years) and 17 age- and intelligence quotient (IQ)-matched Japanese (one female) TD participants (aged 22 to 40 years) read 24 stories; 12 stories featured protagonists with ASD characteristics, and the other 12 featured TD protagonists. Participants read a single sentence at a time and pressed a spacebar to advance to the next sentence. After reading all 24 stories, they were asked to complete a recognition task about the target sentence in each story. Results To investigate episodic memory in ASD, we analyzed encoding based on the reading times for and readability of the stories and retrieval processes based on the accuracy of and response times for sentence recognition. Although the results showed no differences between ASD and TD groups in encoding processes, they did reveal inter-group differences in memory retrieval. Although individuals with ASD demonstrated the same level of accuracy as did TD individuals, their patterns of memory retrieval differed with respect to response times. Conclusions Individuals with ASD more effectively retrieved ASD-congruent than ASD-incongruent sentences, and TD individuals retrieved stories with TD more effectively than stories with ASD protagonists. Thus, similarity between reader and story character had different effects on memory retrieval in the ASD and TD groups. En ligne : http://dx.doi.org/10.1186/2040-2392-4-20 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Episodic memory retrieval for story characters in high-functioning autism [Texte imprimé et/ou numérique] / Hidetsugu KOMEDA, Auteur ; Hirotaka KOSAKA, Auteur ; Daisuke N. SAITO, Auteur ; Keisuke INOHARA, Auteur ; Toshio MUNESUE, Auteur ; Makoto ISHITOBI, Auteur ; Makoto SATO, Auteur ; Hidehiko OKAZAWA, Auteur . - 2013 . - 9 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 9 p. Mots-clés : High-functioning autism  Narrative comprehension  Recognition  Memory retrieval  Similarity Index. décimale : PER Périodiques Résumé : Background The objective of this study was to examine differences in episodic memory retrieval between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals. Previous studies have shown that personality similarities between readers and characters facilitated reading comprehension. Highly extraverted participants read stories featuring extraverted protagonists more easily and judged the outcomes of such stories more rapidly than did less extraverted participants. Similarly, highly neurotic participants judged the outcomes of stories with neurotic protagonists more rapidly than did participants with low levels of neuroticism. However, the impact of the similarity effect on memory retrieval remains unclear. This study tested our ‘similarity hypothesis’, namely that memory retrieval is enhanced when readers with ASD and TD readers read stories featuring protagonists with ASD and with characteristics associated with TD individuals, respectively. Methods Eighteen Japanese individuals (one female) with high-functioning ASD (aged 17 to 40 years) and 17 age- and intelligence quotient (IQ)-matched Japanese (one female) TD participants (aged 22 to 40 years) read 24 stories; 12 stories featured protagonists with ASD characteristics, and the other 12 featured TD protagonists. Participants read a single sentence at a time and pressed a spacebar to advance to the next sentence. After reading all 24 stories, they were asked to complete a recognition task about the target sentence in each story. Results To investigate episodic memory in ASD, we analyzed encoding based on the reading times for and readability of the stories and retrieval processes based on the accuracy of and response times for sentence recognition. Although the results showed no differences between ASD and TD groups in encoding processes, they did reveal inter-group differences in memory retrieval. Although individuals with ASD demonstrated the same level of accuracy as did TD individuals, their patterns of memory retrieval differed with respect to response times. Conclusions Individuals with ASD more effectively retrieved ASD-congruent than ASD-incongruent sentences, and TD individuals retrieved stories with TD more effectively than stories with ASD protagonists. Thus, similarity between reader and story character had different effects on memory retrieval in the ASD and TD groups. En ligne : http://dx.doi.org/10.1186/2040-2392-4-20 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex / S. Hossein FATEMI in Molecular Autism, (June 2013)  

Public ISBD [article]  inMolecular Autism > (June 2013) . - 19 p. Titre : Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex Type de document : Texte imprimé et/ou numérique Auteurs : S. Hossein FATEMI, Auteur ; Timothy D. FOLSOM, Auteur ; Rachel E. KNEELAND, Auteur ; Mahtab K. YOUSEFI, Auteur ; Stephanie B. LIESCH, Auteur ; Paul D. THURAS, Auteur Année de publication : 2013 Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Autism  RAC1  Homer 1  APP  STEP  BA9  Cerebellar vermis  Children  Adults Index. décimale : PER Périodiques Résumé : Background Candidate genes associated with idiopathic forms of autism overlap with other disorders including fragile X syndrome. Our laboratory has previously shown reduction in fragile X mental retardation protein (FMRP) and increase in metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and superior frontal cortex (BA9) of individuals with autism. Methods In the current study we have investigated expression of four targets of FMRP and mGluR5 signaling - homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP) - in the cerebellar vermis and superior frontal cortex (BA9) via SDS-PAGE and western blotting. Data were analyzed based on stratification with respect to age (children and adolescents vs. adults), anatomic region of the brain (BA9 vs. cerebellar vermis), and impact of medications (children and adolescents on medications (n = 4) vs. total children and adolescents (n = 12); adults on medications (n = 6) vs. total adults (n = 12)). Results There were significant increases in RAC1, APP 120 kDa and APP 80 kDa proteins in BA9 of children with autism vs. healthy controls. None of the same proteins were significantly affected in cerebellar vermis of children with autism. In BA9 of adults with autism there were significant increases in RAC1 and STEP 46 kDa and a significant decrease in homer 1 vs. controls. In the vermis of adult subjects with autism, RAC1 was significantly increased while APP 120, STEP 66 kDa, STEP 27 kDa, and homer 1 were significantly decreased when compared with healthy controls. No changes were observed in vermis of children with autism. There was a significant effect of anticonvulsant use on STEP 46 kDa/?-actin and a potential effect on homer 1/NSE, in BA9 of adults with autism. However, no other significant confound effects were observed in this study. Conclusions Our findings provide further evidence of abnormalities in FMRP and mGluR5 signaling partners in brains of individuals with autism and open the door to potential targeted treatments which could help ameliorate the symptoms of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-4-21 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum toxin substrate 1, amyloid beta A4 precursor protein, striatal-enriched protein tyrosine phosphatase, and homer 1, in autism: a postmortem study in cerebellar vermis and superior frontal cortex [Texte imprimé et/ou numérique] / S. Hossein FATEMI, Auteur ; Timothy D. FOLSOM, Auteur ; Rachel E. KNEELAND, Auteur ; Mahtab K. YOUSEFI, Auteur ; Stephanie B. LIESCH, Auteur ; Paul D. THURAS, Auteur . - 2013 . - 19 p. Langues : Anglais (eng) in Molecular Autism > (June 2013) . - 19 p. Mots-clés : Autism  RAC1  Homer 1  APP  STEP  BA9  Cerebellar vermis  Children  Adults Index. décimale : PER Périodiques Résumé : Background Candidate genes associated with idiopathic forms of autism overlap with other disorders including fragile X syndrome. Our laboratory has previously shown reduction in fragile X mental retardation protein (FMRP) and increase in metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and superior frontal cortex (BA9) of individuals with autism. Methods In the current study we have investigated expression of four targets of FMRP and mGluR5 signaling - homer 1, amyloid beta A4 precursor protein (APP), ras-related C3 botulinum toxin substrate 1 (RAC1), and striatal-enriched protein tyrosine phosphatase (STEP) - in the cerebellar vermis and superior frontal cortex (BA9) via SDS-PAGE and western blotting. Data were analyzed based on stratification with respect to age (children and adolescents vs. adults), anatomic region of the brain (BA9 vs. cerebellar vermis), and impact of medications (children and adolescents on medications (n = 4) vs. total children and adolescents (n = 12); adults on medications (n = 6) vs. total adults (n = 12)). Results There were significant increases in RAC1, APP 120 kDa and APP 80 kDa proteins in BA9 of children with autism vs. healthy controls. None of the same proteins were significantly affected in cerebellar vermis of children with autism. In BA9 of adults with autism there were significant increases in RAC1 and STEP 46 kDa and a significant decrease in homer 1 vs. controls. In the vermis of adult subjects with autism, RAC1 was significantly increased while APP 120, STEP 66 kDa, STEP 27 kDa, and homer 1 were significantly decreased when compared with healthy controls. No changes were observed in vermis of children with autism. There was a significant effect of anticonvulsant use on STEP 46 kDa/?-actin and a potential effect on homer 1/NSE, in BA9 of adults with autism. However, no other significant confound effects were observed in this study. Conclusions Our findings provide further evidence of abnormalities in FMRP and mGluR5 signaling partners in brains of individuals with autism and open the door to potential targeted treatments which could help ameliorate the symptoms of autism. En ligne : http://dx.doi.org/10.1186/2040-2392-4-21 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211