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Family-Based Clinical Associations and Functional Characterization of the Serotonin 2A Receptor Gene (HTR2A) in Autism Spectrum Disorder / Ryan M. SMITH in Autism Research, 7-4 (August 2014)
[article]
Titre : Family-Based Clinical Associations and Functional Characterization of the Serotonin 2A Receptor Gene (HTR2A) in Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Ryan M. SMITH, Auteur ; Wesley BANKS, Auteur ; Emily HANSEN, Auteur ; Wolfgang SADEE, Auteur ; Gail E. HERMAN, Auteur Année de publication : 2014 Article en page(s) : p.459-467 Langues : Anglais (eng) Mots-clés : autism serotonin gene expression HTR2A rs6311 monoamine Index. décimale : PER Périodiques Résumé : The serotonin 2A receptor gene (HTR2A) harbors two functional single nucleotide polymorphisms (SNPs) that are frequent in populations of African and European descent; rs6311, which affects mRNA expression, and rs6314, which changes the amino acid sequence of the encoded protein and affects the signaling properties of the receptor. Multiple clinical associations support a role for these SNPs in cognitive and neuropsychiatric phenotypes, although studies in autism spectrum disorder (ASD) remain equivocal. Here, we tested transmission disequilibrium of rs6311 and rs6314 in a cohort of 158 ASD trios (simplex and multiplex), observing significant under-transmission of the minor “A” allele of rs6311 to offspring with ASD (permuted P?=?0.0004). Consistent with our previous findings in the dorsolateral prefrontal cortex of unaffected individuals, rs6311/A decreases expression of HTR2A mRNA with an extended 5? untranslated region (UTR) in the frontopolar cortex in brain samples from 54 ASD patients and controls. Interpreting the clinical results in the context of our mRNA expression analysis, we speculate that any risk associated with rs6311 is conferred by greater expression of the long 5?UTR mRNA isoform. The current study corroborates earlier associations between rs6311 and ASD in a family study, supporting the hypothesis that rs6311 plays a modulatory role in ASD risk. En ligne : http://dx.doi.org/10.1002/aur.1383 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=238
in Autism Research > 7-4 (August 2014) . - p.459-467[article] Family-Based Clinical Associations and Functional Characterization of the Serotonin 2A Receptor Gene (HTR2A) in Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Ryan M. SMITH, Auteur ; Wesley BANKS, Auteur ; Emily HANSEN, Auteur ; Wolfgang SADEE, Auteur ; Gail E. HERMAN, Auteur . - 2014 . - p.459-467.
Langues : Anglais (eng)
in Autism Research > 7-4 (August 2014) . - p.459-467
Mots-clés : autism serotonin gene expression HTR2A rs6311 monoamine Index. décimale : PER Périodiques Résumé : The serotonin 2A receptor gene (HTR2A) harbors two functional single nucleotide polymorphisms (SNPs) that are frequent in populations of African and European descent; rs6311, which affects mRNA expression, and rs6314, which changes the amino acid sequence of the encoded protein and affects the signaling properties of the receptor. Multiple clinical associations support a role for these SNPs in cognitive and neuropsychiatric phenotypes, although studies in autism spectrum disorder (ASD) remain equivocal. Here, we tested transmission disequilibrium of rs6311 and rs6314 in a cohort of 158 ASD trios (simplex and multiplex), observing significant under-transmission of the minor “A” allele of rs6311 to offspring with ASD (permuted P?=?0.0004). Consistent with our previous findings in the dorsolateral prefrontal cortex of unaffected individuals, rs6311/A decreases expression of HTR2A mRNA with an extended 5? untranslated region (UTR) in the frontopolar cortex in brain samples from 54 ASD patients and controls. Interpreting the clinical results in the context of our mRNA expression analysis, we speculate that any risk associated with rs6311 is conferred by greater expression of the long 5?UTR mRNA isoform. The current study corroborates earlier associations between rs6311 and ASD in a family study, supporting the hypothesis that rs6311 plays a modulatory role in ASD risk. En ligne : http://dx.doi.org/10.1002/aur.1383 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=238 Serotonin neuron abnormalities in the BTBR mouse model of autism / Yue-Ping GUO in Autism Research, 10-1 (January 2017)
[article]
Titre : Serotonin neuron abnormalities in the BTBR mouse model of autism Type de document : Texte imprimé et/ou numérique Auteurs : Yue-Ping GUO, Auteur ; Kathryn G. COMMONS, Auteur Article en page(s) : p.66-77 Langues : Anglais (eng) Mots-clés : dorsal raphel median raphe hippocampus monoamine norepinephrine SERT swim Index. décimale : PER Périodiques Résumé : The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) is studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. En ligne : http://dx.doi.org/10.1002/aur.1665 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=302
in Autism Research > 10-1 (January 2017) . - p.66-77[article] Serotonin neuron abnormalities in the BTBR mouse model of autism [Texte imprimé et/ou numérique] / Yue-Ping GUO, Auteur ; Kathryn G. COMMONS, Auteur . - p.66-77.
Langues : Anglais (eng)
in Autism Research > 10-1 (January 2017) . - p.66-77
Mots-clés : dorsal raphel median raphe hippocampus monoamine norepinephrine SERT swim Index. décimale : PER Périodiques Résumé : The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) is studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. En ligne : http://dx.doi.org/10.1002/aur.1665 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=302