Dépouillements

Dysregulation of fragile × mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study / S. Hossein FATEMI in Molecular Autism, (May 2011)  

Public ISBD [article]  inMolecular Autism > (May 2011) . - 11 p. Titre : Dysregulation of fragile × mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study Type de document : Texte imprimé et/ou numérique Auteurs : S. Hossein FATEMI, Auteur ; Timothy D. FOLSOM, Auteur Année de publication : 2011 Article en page(s) : 11 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Fragile × syndrome is caused by loss of function of the fragile × mental retardation 1 (FMR1) gene and shares multiple phenotypes with autism. We have previously found reduced expression of the protein product of FMR1 (FMRP) in vermis of adults with autism. Methods In the current study, we have investigated levels of FMRP in the superior frontal cortex of people with autism and matched controls using Western blot analysis. Because FMRP regulates the translation of multiple genes, we also measured protein levels for downstream molecules metabotropic glutamate receptor 5 (mGluR5) and γ-aminobutyric acid (GABA) A receptor β3 (GABRβ3), as well as glial fibrillary acidic protein (GFAP). Results We observed significantly reduced levels of protein for FMRP in adults with autism, significantly increased levels of protein for mGluR5 in children with autism and significantly increased levels of GFAP in adults and children with autism. We found no change in expression of GABRβ3. Our results for FMRP, mGluR5 and GFAP confirm our previous work in the cerebellar vermis of people with autism. Conclusion These changes may be responsible for cognitive deficits and seizure disorder in people with autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131 [article] Dysregulation of fragile × mental retardation protein and metabotropic glutamate receptor 5 in superior frontal cortex of individuals with autism: a postmortem brain study [Texte imprimé et/ou numérique] / S. Hossein FATEMI, Auteur ; Timothy D. FOLSOM, Auteur . - 2011 . - 11 p. Langues : Anglais (eng) in Molecular Autism > (May 2011) . - 11 p. Index. décimale : PER Périodiques Résumé : Background Fragile × syndrome is caused by loss of function of the fragile × mental retardation 1 (FMR1) gene and shares multiple phenotypes with autism. We have previously found reduced expression of the protein product of FMR1 (FMRP) in vermis of adults with autism. Methods In the current study, we have investigated levels of FMRP in the superior frontal cortex of people with autism and matched controls using Western blot analysis. Because FMRP regulates the translation of multiple genes, we also measured protein levels for downstream molecules metabotropic glutamate receptor 5 (mGluR5) and γ-aminobutyric acid (GABA) A receptor β3 (GABRβ3), as well as glial fibrillary acidic protein (GFAP). Results We observed significantly reduced levels of protein for FMRP in adults with autism, significantly increased levels of protein for mGluR5 in children with autism and significantly increased levels of GFAP in adults and children with autism. We found no change in expression of GABRβ3. Our results for FMRP, mGluR5 and GFAP confirm our previous work in the cerebellar vermis of people with autism. Conclusion These changes may be responsible for cognitive deficits and seizure disorder in people with autism. En ligne : http://dx.doi.org/10.1186/2040-2392-2-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131

Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis / Diane T. STEPHENSON in Molecular Autism, (May 2011)  

Public ISBD [article]  inMolecular Autism > (May 2011) . - 76 p. Titre : Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis Type de document : Texte imprimé et/ou numérique Auteurs : Diane T. STEPHENSON, Auteur ; Sharon M. O'NEILL, Auteur ; Sapna NARAYAN, Auteur ; Aadhya TIWARI, Auteur ; Elizabeth ARNOLD, Auteur ; Harry SAMAROO, Auteur ; Fu DU, Auteur ; Robert RING, Auteur ; Brian M. CAMPBELL, Auteur ; Mathew PLETCHER, Auteur ; Vidita A. VAIDYA, Auteur ; Daniel MORTON, Auteur Année de publication : 2011 Article en page(s) : 76 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background The inbred mouse strain, BTBR T+ tf/J (BTBR) exhibits behavioral deficits which mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse focusing on, neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors. . Methods Forebrains of 8 to 10 week old male BTBR and aged matched C57Bl/6J controls were evaluated by immunohistochemistry using free floating and paraffin embedded sections. Twenty antibodies directed to antigens specific to neurons, synapses and glia were used. Nissl, Timm's and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine were performed to determine hippocampal progenitor proliferation, survival and differentiation and BDNF mRNA was quantified by in situ hybridization. Quantitative image analysis was performed for NG2, doublecortin, NeuroD, GAD67 and PSA-NCAM. Results In midline structures including the region of the absent corpus callosum of BTBR mice, myelin markers myelin basic protein (MBP) and 2' , 3' -cyclic nucleotide 3' -phosphodiesterase (CNPase) were reduced and oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM, and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus and a marked reduction in the number of BrdU positive progenitors Furthermore, a significant and profound reduction in BDNF mRNA in the BTBR dentate gyrus was observed. No significant differences were observed in the expression of acetylcholinesterase, mossy fiber synapses, and immunoreactivities for MAP2, parvalbumin, GAD65 and GAD67. Conclusions We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced adult hippocampal neurogenesis. Of all markers examined, the most distinctive changes were observed in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and doublecortin. Our results are consistent with aberrant development of the nervous system in BTBR mice and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-2-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131 [article] Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis [Texte imprimé et/ou numérique] / Diane T. STEPHENSON, Auteur ; Sharon M. O'NEILL, Auteur ; Sapna NARAYAN, Auteur ; Aadhya TIWARI, Auteur ; Elizabeth ARNOLD, Auteur ; Harry SAMAROO, Auteur ; Fu DU, Auteur ; Robert RING, Auteur ; Brian M. CAMPBELL, Auteur ; Mathew PLETCHER, Auteur ; Vidita A. VAIDYA, Auteur ; Daniel MORTON, Auteur . - 2011 . - 76 p. Langues : Anglais (eng) in Molecular Autism > (May 2011) . - 76 p. Index. décimale : PER Périodiques Résumé : Background The inbred mouse strain, BTBR T+ tf/J (BTBR) exhibits behavioral deficits which mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse focusing on, neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors. . Methods Forebrains of 8 to 10 week old male BTBR and aged matched C57Bl/6J controls were evaluated by immunohistochemistry using free floating and paraffin embedded sections. Twenty antibodies directed to antigens specific to neurons, synapses and glia were used. Nissl, Timm's and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine were performed to determine hippocampal progenitor proliferation, survival and differentiation and BDNF mRNA was quantified by in situ hybridization. Quantitative image analysis was performed for NG2, doublecortin, NeuroD, GAD67 and PSA-NCAM. Results In midline structures including the region of the absent corpus callosum of BTBR mice, myelin markers myelin basic protein (MBP) and 2' , 3' -cyclic nucleotide 3' -phosphodiesterase (CNPase) were reduced and oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM, and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus and a marked reduction in the number of BrdU positive progenitors Furthermore, a significant and profound reduction in BDNF mRNA in the BTBR dentate gyrus was observed. No significant differences were observed in the expression of acetylcholinesterase, mossy fiber synapses, and immunoreactivities for MAP2, parvalbumin, GAD65 and GAD67. Conclusions We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced adult hippocampal neurogenesis. Of all markers examined, the most distinctive changes were observed in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and doublecortin. Our results are consistent with aberrant development of the nervous system in BTBR mice and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-2-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131

A quantitative association study of SLC25A12 and restricted repetitive behavior traits in autism spectrum disorders / Soo-Jeong KIM in Molecular Autism, (May 2011)  

Public ISBD [article]  inMolecular Autism > (May 2011) . - 48 p. Titre : A quantitative association study of SLC25A12 and restricted repetitive behavior traits in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Soo-Jeong KIM, Auteur ; Raquel M. SILVA, Auteur ; Cindi G. FLORES, Auteur ; Suma JACOB, Auteur ; Stephen GUTER, Auteur ; Gregory VALCANTE, Auteur ; Annette M. ZAYTOUN, Auteur ; Edwin H. Jr COOK, Auteur ; Judith A. BADNER, Auteur Année de publication : 2011 Article en page(s) : 48 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background SLC25A12 was previously identified in a linkage directed association analysis in autism. In this study, we investigated the relationship between three SLC25A12 single nucleotide polymorphisms (SNPs) (rs2056202, rs908670 and rs2292813) and restricted repetitive behavior (RRB) traits in autism spectrum disorders (ASDs), based on a positive correlation between the G allele of rs2056202 and an RRB subdomain score on the Autism Diagnostic Interview-Revised (ADI-R). Methods We used the Repetitive Behavior Scale-Revised (RBS-R) as a quantitative RRB measure, and conducted linear regression analyses for individual SNPs and a previously identified haplotype (rs2056202-rs2292813). We examined associations in our UIC-UF sample (179 unrelated individuals), and then attempted to replicate our findings in the Simons Simplex Collection (SSC) sample (720 families). Results In the UIC-UF sample, three RBS-R scores (ritualistic/sameness/sum) showed positive associations with the A allele of rs2292813 (p=0.006-0.012), and with rs2056202-rs2292813 haplotype (omnibus test p=0.025-0.040). The SSC sample revealed positive associations between the A allele of rs2056202 and four RBS-R scores (stereotyped/sameness/restricted/sum, p=0.006-0.010), between the A allele of rs908670 and three RBS-R scores (stereotyped/self-injurious/sum, p=0.003-0.015), and between rs2056202-rs2292813 haplotype and RBS-R scores (stereotyped/self-injurious/compulsive/sameness/restricted/sum, omnibus test p=0.002-0.028). Taken together, the A alleles of rs2056202 and rs2292813 were consistently positively associated with RRB traits in both UIC-UF and SSC samples, but the most significant SNP-phenotype association varied in each dataset. Conclusions This study confirmed an association between SLC25A12 and RRB traits in ASDs, but the direction of the association was different from the initial study. This may be because of the examined SLC25A12 SNPs being in linkage disequilibrium (LD) with another risk allele as well as genetic/phenotypic heterogeneity of the ASD samples across studies. En ligne : http://dx.doi.org/10.1186/2040-2392-2-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131 [article] A quantitative association study of SLC25A12 and restricted repetitive behavior traits in autism spectrum disorders [Texte imprimé et/ou numérique] / Soo-Jeong KIM, Auteur ; Raquel M. SILVA, Auteur ; Cindi G. FLORES, Auteur ; Suma JACOB, Auteur ; Stephen GUTER, Auteur ; Gregory VALCANTE, Auteur ; Annette M. ZAYTOUN, Auteur ; Edwin H. Jr COOK, Auteur ; Judith A. BADNER, Auteur . - 2011 . - 48 p. Langues : Anglais (eng) in Molecular Autism > (May 2011) . - 48 p. Index. décimale : PER Périodiques Résumé : Background SLC25A12 was previously identified in a linkage directed association analysis in autism. In this study, we investigated the relationship between three SLC25A12 single nucleotide polymorphisms (SNPs) (rs2056202, rs908670 and rs2292813) and restricted repetitive behavior (RRB) traits in autism spectrum disorders (ASDs), based on a positive correlation between the G allele of rs2056202 and an RRB subdomain score on the Autism Diagnostic Interview-Revised (ADI-R). Methods We used the Repetitive Behavior Scale-Revised (RBS-R) as a quantitative RRB measure, and conducted linear regression analyses for individual SNPs and a previously identified haplotype (rs2056202-rs2292813). We examined associations in our UIC-UF sample (179 unrelated individuals), and then attempted to replicate our findings in the Simons Simplex Collection (SSC) sample (720 families). Results In the UIC-UF sample, three RBS-R scores (ritualistic/sameness/sum) showed positive associations with the A allele of rs2292813 (p=0.006-0.012), and with rs2056202-rs2292813 haplotype (omnibus test p=0.025-0.040). The SSC sample revealed positive associations between the A allele of rs2056202 and four RBS-R scores (stereotyped/sameness/restricted/sum, p=0.006-0.010), between the A allele of rs908670 and three RBS-R scores (stereotyped/self-injurious/sum, p=0.003-0.015), and between rs2056202-rs2292813 haplotype and RBS-R scores (stereotyped/self-injurious/compulsive/sameness/restricted/sum, omnibus test p=0.002-0.028). Taken together, the A alleles of rs2056202 and rs2292813 were consistently positively associated with RRB traits in both UIC-UF and SSC samples, but the most significant SNP-phenotype association varied in each dataset. Conclusions This study confirmed an association between SLC25A12 and RRB traits in ASDs, but the direction of the association was different from the initial study. This may be because of the examined SLC25A12 SNPs being in linkage disequilibrium (LD) with another risk allele as well as genetic/phenotypic heterogeneity of the ASD samples across studies. En ligne : http://dx.doi.org/10.1186/2040-2392-2-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131

Gene expression analysis in lymphoblasts derived from patients with autism spectrum disorder / Yuka YASUDA in Molecular Autism, (May 2011)  

Public ISBD [article]  inMolecular Autism > (May 2011) . - 8 p. Titre : Gene expression analysis in lymphoblasts derived from patients with autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Yuka YASUDA, Auteur ; Ryota HASHIMOTO, Auteur ; Hidenaga YAMAMORI, Auteur ; Kazutaka OHI, Auteur ; Motoyuki FUKUMOTO, Auteur ; Satomi UMEDA-YANO, Auteur ; Ikuko MOHRI, Auteur ; Akira ITO, Auteur ; Masako TANIIKE, Auteur ; Masatoshi TAKEDA, Auteur Année de publication : 2011 Article en page(s) : 8 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background The autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that result in severe and pervasive impairment in the development of reciprocal social interaction and verbal and nonverbal communication skills. In addition, individuals with ASD have stereotypical behavior, interests and activities. Rare mutations of some genes, such as neuroligin (NLGN) 3/4, neurexin (NRXN) 1, SHANK3, MeCP2 and NHE9, have been reported to be associated with ASD. In the present study, we investigated whether alterations in mRNA expression levels of these genes could be found in lymphoblastoid cell lines derived from patients with ASD. Methods We measured mRNA expression levels of NLGN3/4, NRXN1, SHANK3, MeCP2, NHE9 and AKT1 in lymphoblastoid cells from 35 patients with ASD and 35 healthy controls, as well as from 45 patients with schizophrenia and 45 healthy controls, using real-time quantitative reverse transcriptase polymerase chain reaction assays. Results The mRNA expression levels of NLGN3 and SHANK3 normalized by β-actin or TBP were significantly decreased in the individuals with ASD compared to controls, whereas no difference was found in the mRNA expression level of MeCP2, NHE9 or AKT1. However, normalized NLGN3 and SHANK3 gene expression levels were not altered in patients with schizophrenia, and expression levels of NLGN4 and NRXN1 mRNA were not quantitatively measurable in lymphoblastoid cells. Conclusions Our results provide evidence that the NLGN3 and SHANK3 genes may be differentially expressed in lymphoblastoid cell lines from individuals with ASD compared to those from controls. These findings suggest the possibility that decreased mRNA expression levels of these genes might be involved in the pathophysiology of ASD in a substantial population of ASD patients. En ligne : http://dx.doi.org/10.1186/2040-2392-2-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131 [article] Gene expression analysis in lymphoblasts derived from patients with autism spectrum disorder [Texte imprimé et/ou numérique] / Yuka YASUDA, Auteur ; Ryota HASHIMOTO, Auteur ; Hidenaga YAMAMORI, Auteur ; Kazutaka OHI, Auteur ; Motoyuki FUKUMOTO, Auteur ; Satomi UMEDA-YANO, Auteur ; Ikuko MOHRI, Auteur ; Akira ITO, Auteur ; Masako TANIIKE, Auteur ; Masatoshi TAKEDA, Auteur . - 2011 . - 8 p. Langues : Anglais (eng) in Molecular Autism > (May 2011) . - 8 p. Index. décimale : PER Périodiques Résumé : Background The autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that result in severe and pervasive impairment in the development of reciprocal social interaction and verbal and nonverbal communication skills. In addition, individuals with ASD have stereotypical behavior, interests and activities. Rare mutations of some genes, such as neuroligin (NLGN) 3/4, neurexin (NRXN) 1, SHANK3, MeCP2 and NHE9, have been reported to be associated with ASD. In the present study, we investigated whether alterations in mRNA expression levels of these genes could be found in lymphoblastoid cell lines derived from patients with ASD. Methods We measured mRNA expression levels of NLGN3/4, NRXN1, SHANK3, MeCP2, NHE9 and AKT1 in lymphoblastoid cells from 35 patients with ASD and 35 healthy controls, as well as from 45 patients with schizophrenia and 45 healthy controls, using real-time quantitative reverse transcriptase polymerase chain reaction assays. Results The mRNA expression levels of NLGN3 and SHANK3 normalized by β-actin or TBP were significantly decreased in the individuals with ASD compared to controls, whereas no difference was found in the mRNA expression level of MeCP2, NHE9 or AKT1. However, normalized NLGN3 and SHANK3 gene expression levels were not altered in patients with schizophrenia, and expression levels of NLGN4 and NRXN1 mRNA were not quantitatively measurable in lymphoblastoid cells. Conclusions Our results provide evidence that the NLGN3 and SHANK3 genes may be differentially expressed in lymphoblastoid cell lines from individuals with ASD compared to those from controls. These findings suggest the possibility that decreased mRNA expression levels of these genes might be involved in the pathophysiology of ASD in a substantial population of ASD patients. En ligne : http://dx.doi.org/10.1186/2040-2392-2-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131