Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging / J. ELLEGOOD in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 24p. 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 [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

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