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Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging / J. ELLEGOOD in Molecular Autism, 9 (2018)
[article]
Titre : Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging Type de document : Texte imprimé et/ou numérique Auteurs : J. ELLEGOOD, Auteur ; Y. YEE, Auteur ; T. M. KERR, Auteur ; C. L. MULLER, Auteur ; R. D. BLAKELY, Auteur ; R. M. HENKELMAN, Auteur ; J. VEENSTRA-VANDERWEELE, Auteur ; J. P. LERCH, Auteur Article en page(s) : 24p. Langues : Anglais (eng) Mots-clés : Animals Brain/diagnostic imaging/metabolism Female Magnetic Resonance Imaging Male Mice Mice, Inbred C57BL Mutation Neurons/metabolism Serotonin/metabolism Serotonin Plasma Membrane Transport Proteins/genetics/metabolism 5-ht 5htt Brain Dorsal raphe Magnetic resonance imaging Neurodevelopment Serotonin Slc6a4 Index. décimale : PER Périodiques Résumé : Background: The serotonin (5-HT) system has long been implicated in autism spectrum disorder (ASD) as indicated by elevated whole blood and platelet 5-HT, altered platelet and brain receptor and transporter binding, and genetic linkage and association findings. Based upon work in genetically modified mice, 5-HT is known to influence several aspects of brain development, but systematic neuroimaging studies have not previously been reported. In particular, the 5-HT transporter (serotonin transporter, SERT; 5-HTT) gene, Slc6a4, has been extensively studied. Methods: Using a 7-T MRI and deformation-based morphometry, we assessed neuroanatomical differences in an Slc6a4 knockout mouse on a C57BL/6 genetic background, along with an Slc6a4 Ala56 knockin mouse on two different genetic backgrounds (129S and C57BL/6). Results: Individually (same sex, same background, same genotype), the only differences found were in the female Slc6a4 knockout mouse; all the others had no significant differences. However, an analysis of variance across the whole study sample revealed a significant effect of Slc6a4 on the amygdala, thalamus, dorsal raphe nucleus, and lateral and frontal cortices. Conclusions: This work shows that an increase or decrease in SERT function has a significant effect on the neuroanatomy in 5-HT relevant regions, particularly the raphe nuclei. Notably, the Slc6a4 Ala56 knockin alone appears to have an insignificant, but suggestive, effect compared to the KO, which is consistent with Slc6a4 function. Despite the small number of 5-HT neurons and their localization to the brainstem, it is clear that 5-HT plays an important role in neuroanatomical organization. En ligne : https://dx.doi.org/10.1186/s13229-018-0210-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 24p.[article] Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging [Texte imprimé et/ou numérique] / J. ELLEGOOD, Auteur ; Y. YEE, Auteur ; T. M. KERR, Auteur ; C. L. MULLER, Auteur ; R. D. BLAKELY, Auteur ; R. M. HENKELMAN, Auteur ; J. VEENSTRA-VANDERWEELE, Auteur ; J. P. LERCH, Auteur . - 24p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 24p.
Mots-clés : Animals Brain/diagnostic imaging/metabolism Female Magnetic Resonance Imaging Male Mice Mice, Inbred C57BL Mutation Neurons/metabolism Serotonin/metabolism Serotonin Plasma Membrane Transport Proteins/genetics/metabolism 5-ht 5htt Brain Dorsal raphe Magnetic resonance imaging Neurodevelopment Serotonin Slc6a4 Index. décimale : PER Périodiques Résumé : Background: The serotonin (5-HT) system has long been implicated in autism spectrum disorder (ASD) as indicated by elevated whole blood and platelet 5-HT, altered platelet and brain receptor and transporter binding, and genetic linkage and association findings. Based upon work in genetically modified mice, 5-HT is known to influence several aspects of brain development, but systematic neuroimaging studies have not previously been reported. In particular, the 5-HT transporter (serotonin transporter, SERT; 5-HTT) gene, Slc6a4, has been extensively studied. Methods: Using a 7-T MRI and deformation-based morphometry, we assessed neuroanatomical differences in an Slc6a4 knockout mouse on a C57BL/6 genetic background, along with an Slc6a4 Ala56 knockin mouse on two different genetic backgrounds (129S and C57BL/6). Results: Individually (same sex, same background, same genotype), the only differences found were in the female Slc6a4 knockout mouse; all the others had no significant differences. However, an analysis of variance across the whole study sample revealed a significant effect of Slc6a4 on the amygdala, thalamus, dorsal raphe nucleus, and lateral and frontal cortices. Conclusions: This work shows that an increase or decrease in SERT function has a significant effect on the neuroanatomy in 5-HT relevant regions, particularly the raphe nuclei. Notably, the Slc6a4 Ala56 knockin alone appears to have an insignificant, but suggestive, effect compared to the KO, which is consistent with Slc6a4 function. Despite the small number of 5-HT neurons and their localization to the brainstem, it is clear that 5-HT plays an important role in neuroanatomical organization. En ligne : https://dx.doi.org/10.1186/s13229-018-0210-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder? / Lauren C. SHUFFREY in Autism Research, 10-8 (August 2017)
[article]
Titre : Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder? Type de document : Texte imprimé et/ou numérique Auteurs : Lauren C. SHUFFREY, Auteur ; Stephen J. GUTER, Auteur ; Shannon DELANEY, Auteur ; Suma JACOB, Auteur ; George M. ANDERSON, Auteur ; James S. SUTCLIFFE, Auteur ; Edwin H. Jr COOK, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur Article en page(s) : p.1417-1423 Langues : Anglais (eng) Mots-clés : serotonin 5-HT autism spectrum disorder hyperserotonemia Index. décimale : PER Périodiques Résumé : Approximately 30% of individuals with autism spectrum disorder (ASD) have elevated whole blood serotonin (5-HT) levels. Genetic linkage and association studies of ASD and of whole blood 5-HT levels as a quantitative trait have revealed sexual dimorphism. Few studies have examined the presence of a sex difference on hyperserotonemia within ASD. To assess whether the rate of hyperserotonemia is different in males than in females with ASD, we measured whole blood 5-HT levels in 292 children and adolescents with ASD, the largest sample in which this biomarker has been assessed. Based upon previous work suggesting that hyperserotonemia is more common prior to puberty, we focused our analysis on the 182 pre-pubertal children with ASD. 42% of pre-pubertal participants were within the hyperserotonemia range. In this population, we found that males were significantly more likely to manifest hyperserotonemia than females (P?=?0.03). As expected, no significant difference was found in the post-pubertal population. Additional work will be needed to replicate this intriguing finding and to understand whether it could potentially explain differences in patterns of ASD risk between males and females. En ligne : http://dx.doi.org/10.1002/aur.1791 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=310
in Autism Research > 10-8 (August 2017) . - p.1417-1423[article] Is there sexual dimorphism of hyperserotonemia in autism spectrum disorder? [Texte imprimé et/ou numérique] / Lauren C. SHUFFREY, Auteur ; Stephen J. GUTER, Auteur ; Shannon DELANEY, Auteur ; Suma JACOB, Auteur ; George M. ANDERSON, Auteur ; James S. SUTCLIFFE, Auteur ; Edwin H. Jr COOK, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur . - p.1417-1423.
Langues : Anglais (eng)
in Autism Research > 10-8 (August 2017) . - p.1417-1423
Mots-clés : serotonin 5-HT autism spectrum disorder hyperserotonemia Index. décimale : PER Périodiques Résumé : Approximately 30% of individuals with autism spectrum disorder (ASD) have elevated whole blood serotonin (5-HT) levels. Genetic linkage and association studies of ASD and of whole blood 5-HT levels as a quantitative trait have revealed sexual dimorphism. Few studies have examined the presence of a sex difference on hyperserotonemia within ASD. To assess whether the rate of hyperserotonemia is different in males than in females with ASD, we measured whole blood 5-HT levels in 292 children and adolescents with ASD, the largest sample in which this biomarker has been assessed. Based upon previous work suggesting that hyperserotonemia is more common prior to puberty, we focused our analysis on the 182 pre-pubertal children with ASD. 42% of pre-pubertal participants were within the hyperserotonemia range. In this population, we found that males were significantly more likely to manifest hyperserotonemia than females (P?=?0.03). As expected, no significant difference was found in the post-pubertal population. Additional work will be needed to replicate this intriguing finding and to understand whether it could potentially explain differences in patterns of ASD risk between males and females. En ligne : http://dx.doi.org/10.1002/aur.1791 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=310 Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder / Sarah MARLER in Journal of Autism and Developmental Disorders, 46-3 (March 2016)
[article]
Titre : Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Sarah MARLER, Auteur ; Bradley J. FERGUSON, Auteur ; Evon BATEY LEE, Auteur ; Brittany PETERS, Auteur ; Kent C. WILLIAMS, Auteur ; Erin MCDONNELL, Auteur ; Eric A. MACKLIN, Auteur ; Pat LEVITT, Auteur ; Catherine HAGAN GILLESPIE, Auteur ; George M. ANDERSON, Auteur ; Kara Gross MARGOLIS, Auteur ; David Q. BEVERSDORF, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur Article en page(s) : p.1124-1130 Langues : Anglais (eng) Mots-clés : Serotonin 5-HT Gastrointestinal (GI) IL-6 Medical comorbidities Autism Treatment Network Index. décimale : PER Périodiques Résumé : Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD. En ligne : http://dx.doi.org/10.1007/s10803-015-2646-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282
in Journal of Autism and Developmental Disorders > 46-3 (March 2016) . - p.1124-1130[article] Brief Report: Whole Blood Serotonin Levels and Gastrointestinal Symptoms in Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Sarah MARLER, Auteur ; Bradley J. FERGUSON, Auteur ; Evon BATEY LEE, Auteur ; Brittany PETERS, Auteur ; Kent C. WILLIAMS, Auteur ; Erin MCDONNELL, Auteur ; Eric A. MACKLIN, Auteur ; Pat LEVITT, Auteur ; Catherine HAGAN GILLESPIE, Auteur ; George M. ANDERSON, Auteur ; Kara Gross MARGOLIS, Auteur ; David Q. BEVERSDORF, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur . - p.1124-1130.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 46-3 (March 2016) . - p.1124-1130
Mots-clés : Serotonin 5-HT Gastrointestinal (GI) IL-6 Medical comorbidities Autism Treatment Network Index. décimale : PER Périodiques Résumé : Elevated whole blood serotonin levels are observed in more than 25 % of children with autism spectrum disorder (ASD). Co-occurring gastrointestinal (GI) symptoms are also common in ASD but have not previously been examined in relationship with hyperserotonemia, despite the synthesis of serotonin in the gut. In 82 children and adolescents with ASD, we observed a correlation between a quantitative measure of lower GI symptoms and whole blood serotonin levels. No significant association was seen between functional constipation diagnosis and serotonin levels in the hyperserotonemia range, suggesting that this correlation is not driven by a single subgroup. More specific assessment of gut function, including the microbiome, will be necessary to evaluate the contribution of gut physiology to serotonin levels in ASD. En ligne : http://dx.doi.org/10.1007/s10803-015-2646-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282 Commentary on "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" / George M. ANDERSON in Molecular Autism, 7 (2016)
[article]
Titre : Commentary on "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" Type de document : Texte imprimé et/ou numérique Auteurs : George M. ANDERSON, Auteur ; Edwin H. Jr COOK, Auteur Article en page(s) : 20p. Langues : Anglais (eng) Mots-clés : 5-ht Autism Hyperserotonemia Platelet aggregation Platelet count Platelet functioning Platelet release Serotonin Index. décimale : PER Périodiques Résumé : We comment on the recent report entitled "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" [Molecular Autism 2015;6:57]. We find it commendable that the authors have investigated platelet factors potentially involved in the well-replicated observation of platelet hyperserotonemia in autism. However, we believe the results need a fuller discussion in the context of prior studies, think that certain aspects of the interpretation need to be reassessed, and attempt to provide a framework for further research in this area. En ligne : http://dx.doi.org/10.1186/s13229-016-0086-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328
in Molecular Autism > 7 (2016) . - 20p.[article] Commentary on "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" [Texte imprimé et/ou numérique] / George M. ANDERSON, Auteur ; Edwin H. Jr COOK, Auteur . - 20p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 20p.
Mots-clés : 5-ht Autism Hyperserotonemia Platelet aggregation Platelet count Platelet functioning Platelet release Serotonin Index. décimale : PER Périodiques Résumé : We comment on the recent report entitled "Platelet Studies in Autism Spectrum Disorder Patients and First-Degree Relatives" [Molecular Autism 2015;6:57]. We find it commendable that the authors have investigated platelet factors potentially involved in the well-replicated observation of platelet hyperserotonemia in autism. However, we believe the results need a fuller discussion in the context of prior studies, think that certain aspects of the interpretation need to be reassessed, and attempt to provide a framework for further research in this area. En ligne : http://dx.doi.org/10.1186/s13229-016-0086-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 Organism Models: Choosing the Right Model / Nicolas LEVY
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