1928 recherche sur le mot-clé 'Humans'

Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice / Stijn VAN DE SOMPELE ; Clemence LIGNEUL ; Camille CHATELAIN ; Christophe BARREA ; Jason P. LERCH ; Beatrice M. FILIPPI ; Serpil ALKAN ; Elfride DE BAERE ; Jamie JOHNSTON ; Steven J. CLAPCOTE in Molecular Autism, 16 (2025)  

Public ISBD [article]  inMolecular Autism > 16 (2025) . - 14 Titre : Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice Type de document : texte imprimé Auteurs : Stijn VAN DE SOMPELE, Auteur ; Clemence LIGNEUL, Auteur ; Camille CHATELAIN, Auteur ; Christophe BARREA, Auteur ; Jason P. LERCH, Auteur ; Beatrice M. FILIPPI, Auteur ; Serpil ALKAN, Auteur ; Elfride DE BAERE, Auteur ; Jamie JOHNSTON, Auteur ; Steven J. CLAPCOTE, Auteur Article en page(s) : 14 Langues : Anglais (eng) Mots-clés : Animals  Humans  Male  Female  Mice  Autistic Disorder/genetics  Alleles  Intellectual Disability/genetics  Pedigree  Autism Spectrum Disorder/genetics  Child  Phenotype  Behavior, Animal  Membrane Proteins/genetics  Social Behavior  Mutation  Adult  Child, Preschool  DNA-Binding Proteins  Autism spectrum disorder  Intellectual disability  Olfactory behavior  Pdzd8  Social discrimination  approved by Ghent University Ethical Committee. The affected individuals were  recruited to the study with the informed consent of their mother using a process  that adhered to the tenets of the Declaration of Helsinki. The mouse experiments  were conducted in compliance with the UK Animals (Scientific Procedures) Act 1986  under UK Home Office licences and approved by the Animal Welfare and Ethical  Review Body at the University of Leeds. Consent for publication: Written consent  for publication of case reports and images pertaining to the affected individuals  was obtained from their mother. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual developmental disorder with autism and dysmorphic facies (IDDADF) is a rare syndromic intellectual disability (ID) caused by homozygous disruption of PDZD8 (PDZ domain-containing protein 8), an integral endoplasmic reticulum (ER) protein. All four previously identified IDDADF cases exhibit autistic behavior, with autism spectrum disorder (ASD) diagnosed in three cases. To determine whether autistic behavior is a common outcome of PDZD8 disruption, we studied a third family with biallelic mutation of PDZD8 (family C) and further characterized PDZD8-deficient (Pdzd8(tm1b)) mice that exhibit stereotyped motor behavior relevant to ASD. METHODS: Homozygosity mapping, whole-exome sequencing, and cosegregation analysis were used to identify the PDZD8 variant responsible for IDDADF, including diagnoses of ASD, in consanguineous family C. To assess the in vivo effect of PDZD8 disruption on social responses and related phenotypes, behavioral, structural magnetic resonance imaging, and microscopy analyses were conducted on the Pdzd8(tm1b) mouse line. Metabolic activity was profiled using sealed metabolic cages. RESULTS: The discovery of a third family with IDDADF caused by biallelic disruption of PDZD8 permitted identification of a core clinical phenotype consisting of developmental delay, ID, autism, and facial dysmorphism. In addition to impairments in social recognition and social odor discrimination, Pdzd8(tm1b) mice exhibit increases in locomotor activity (dark phase only) and metabolic rate (both lights-on and dark phases), and decreased plasma triglyceride in males. In the brain, Pdzd8(tm1b) mice exhibit increased levels of accessory olfactory bulb volume, primary olfactory cortex volume, dendritic spine density, and ER stress- and mitochondrial fusion-related transcripts, as well as decreased levels of cerebellar nuclei volume and adult neurogenesis. LIMITATIONS: The total number of known cases of PDZD8-related IDDADF remains low. Some mouse experiments in the study did not use balanced numbers of males and females. The assessment of ER stress and mitochondrial fusion markers did not extend beyond mRNA levels. CONCLUSIONS: Our finding that the Pdzd8(tm1b) mouse model and all six known cases of IDDADF exhibit autistic behavior, with ASD diagnosed in five cases, identifies this trait as a common outcome of biallelic disruption of PDZD8 in humans and mice. Other abnormalities exhibited by Pdzd8(tm1b) mice suggest that the range of comorbidities associated with PDZD8 deficiency may be wider than presently recognized. En ligne : https://dx.doi.org/10.1186/s13229-025-00650-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice [texte imprimé] / Stijn VAN DE SOMPELE, Auteur ; Clemence LIGNEUL, Auteur ; Camille CHATELAIN, Auteur ; Christophe BARREA, Auteur ; Jason P. LERCH, Auteur ; Beatrice M. FILIPPI, Auteur ; Serpil ALKAN, Auteur ; Elfride DE BAERE, Auteur ; Jamie JOHNSTON, Auteur ; Steven J. CLAPCOTE, Auteur . - 14. Langues : Anglais (eng) in Molecular Autism > 16 (2025) . - 14 Mots-clés : Animals  Humans  Male  Female  Mice  Autistic Disorder/genetics  Alleles  Intellectual Disability/genetics  Pedigree  Autism Spectrum Disorder/genetics  Child  Phenotype  Behavior, Animal  Membrane Proteins/genetics  Social Behavior  Mutation  Adult  Child, Preschool  DNA-Binding Proteins  Autism spectrum disorder  Intellectual disability  Olfactory behavior  Pdzd8  Social discrimination  approved by Ghent University Ethical Committee. The affected individuals were  recruited to the study with the informed consent of their mother using a process  that adhered to the tenets of the Declaration of Helsinki. The mouse experiments  were conducted in compliance with the UK Animals (Scientific Procedures) Act 1986  under UK Home Office licences and approved by the Animal Welfare and Ethical  Review Body at the University of Leeds. Consent for publication: Written consent  for publication of case reports and images pertaining to the affected individuals  was obtained from their mother. Competing interests: The authors declare no  competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Intellectual developmental disorder with autism and dysmorphic facies (IDDADF) is a rare syndromic intellectual disability (ID) caused by homozygous disruption of PDZD8 (PDZ domain-containing protein 8), an integral endoplasmic reticulum (ER) protein. All four previously identified IDDADF cases exhibit autistic behavior, with autism spectrum disorder (ASD) diagnosed in three cases. To determine whether autistic behavior is a common outcome of PDZD8 disruption, we studied a third family with biallelic mutation of PDZD8 (family C) and further characterized PDZD8-deficient (Pdzd8(tm1b)) mice that exhibit stereotyped motor behavior relevant to ASD. METHODS: Homozygosity mapping, whole-exome sequencing, and cosegregation analysis were used to identify the PDZD8 variant responsible for IDDADF, including diagnoses of ASD, in consanguineous family C. To assess the in vivo effect of PDZD8 disruption on social responses and related phenotypes, behavioral, structural magnetic resonance imaging, and microscopy analyses were conducted on the Pdzd8(tm1b) mouse line. Metabolic activity was profiled using sealed metabolic cages. RESULTS: The discovery of a third family with IDDADF caused by biallelic disruption of PDZD8 permitted identification of a core clinical phenotype consisting of developmental delay, ID, autism, and facial dysmorphism. In addition to impairments in social recognition and social odor discrimination, Pdzd8(tm1b) mice exhibit increases in locomotor activity (dark phase only) and metabolic rate (both lights-on and dark phases), and decreased plasma triglyceride in males. In the brain, Pdzd8(tm1b) mice exhibit increased levels of accessory olfactory bulb volume, primary olfactory cortex volume, dendritic spine density, and ER stress- and mitochondrial fusion-related transcripts, as well as decreased levels of cerebellar nuclei volume and adult neurogenesis. LIMITATIONS: The total number of known cases of PDZD8-related IDDADF remains low. Some mouse experiments in the study did not use balanced numbers of males and females. The assessment of ER stress and mitochondrial fusion markers did not extend beyond mRNA levels. CONCLUSIONS: Our finding that the Pdzd8(tm1b) mouse model and all six known cases of IDDADF exhibit autistic behavior, with ASD diagnosed in five cases, identifies this trait as a common outcome of biallelic disruption of PDZD8 in humans and mice. Other abnormalities exhibited by Pdzd8(tm1b) mice suggest that the range of comorbidities associated with PDZD8 deficiency may be wider than presently recognized. En ligne : https://dx.doi.org/10.1186/s13229-025-00650-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

Attentional shifting differences in autism: Domain general, domain specific or both? / Simona SKRIPKAUSKAITE in Autism, 25-6 (August 2021)  

Public ISBD [article]  inAutism > 25-6 (August 2021) . - p.1721-1733 Titre : Attentional shifting differences in autism: Domain general, domain specific or both? Type de document : texte imprimé Auteurs : Simona SKRIPKAUSKAITE, Auteur ; Lance SLADE, Auteur ; Jennifer L. MAYER, Auteur Article en page(s) : p.1721-1733 Langues : Anglais (eng) Mots-clés : Adult  Attention  Autism Spectrum Disorder  Autistic Disorder  Humans  adults  autism  eye tracking  gap–overlap  saccadic latencies Index. décimale : PER Périodiques Résumé : Previous research has shown that autistic individuals look at other people less and orient to them more slowly than others. Yet, it is still unclear if this represents general visual differences (e.g. slower looking at any new information, social or not) or a uniquely social difference (e.g. only slower looking to humans but not objects). Here, we aimed to examine how quickly autistic and non-autistic adults look to and away from social (i.e. faces) and non-social information (i.e. squares and houses). We used an attentional shifting task with two images where sometimes the first image disappears before the new image appears (makes it easier to notice the new image) and other times it stays on the screen when the new image appears. In Experiment 1, we showed schematic faces and squares to 27 autistic and 26 non-autistic adults, and in Experiment 2, we showed photographs of faces and houses to 18 autistic and 17 non-autistic adults. In general, autistic adults looked at the new non-social or social images similarly to non-autistic adults. Yet, only autistic adults looked at new social information faster when the first image disappeared before the new image appeared. This shows that autistic individuals may find it easier to notice new social information if their attention is not already occupied. En ligne : http://dx.doi.org/10.1177/13623613211001619 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=451 [article] Attentional shifting differences in autism: Domain general, domain specific or both? [texte imprimé] / Simona SKRIPKAUSKAITE, Auteur ; Lance SLADE, Auteur ; Jennifer L. MAYER, Auteur . - p.1721-1733. Langues : Anglais (eng) in Autism > 25-6 (August 2021) . - p.1721-1733 Mots-clés : Adult  Attention  Autism Spectrum Disorder  Autistic Disorder  Humans  adults  autism  eye tracking  gap–overlap  saccadic latencies Index. décimale : PER Périodiques Résumé : Previous research has shown that autistic individuals look at other people less and orient to them more slowly than others. Yet, it is still unclear if this represents general visual differences (e.g. slower looking at any new information, social or not) or a uniquely social difference (e.g. only slower looking to humans but not objects). Here, we aimed to examine how quickly autistic and non-autistic adults look to and away from social (i.e. faces) and non-social information (i.e. squares and houses). We used an attentional shifting task with two images where sometimes the first image disappears before the new image appears (makes it easier to notice the new image) and other times it stays on the screen when the new image appears. In Experiment 1, we showed schematic faces and squares to 27 autistic and 26 non-autistic adults, and in Experiment 2, we showed photographs of faces and houses to 18 autistic and 17 non-autistic adults. In general, autistic adults looked at the new non-social or social images similarly to non-autistic adults. Yet, only autistic adults looked at new social information faster when the first image disappeared before the new image appeared. This shows that autistic individuals may find it easier to notice new social information if their attention is not already occupied. En ligne : http://dx.doi.org/10.1177/13623613211001619 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=451

Attentional shifting differences in autism: Domain general, domain specific or both? / Simona SKRIPKAUSKAITE in Autism, 26-6 (August 2022)  

Public ISBD [article]  inAutism > 26-6 (August 2022) . - p.1721-1733 Titre : Attentional shifting differences in autism: Domain general, domain specific or both? Type de document : texte imprimé Auteurs : Simona SKRIPKAUSKAITE, Auteur ; Lance SLADE, Auteur ; Jennifer L. MAYER, Auteur Article en page(s) : p.1721-1733 Langues : Anglais (eng) Mots-clés : Adult  Attention  Autism Spectrum Disorder  Autistic Disorder  Humans  adults  autism  eye tracking  gap–overlap  saccadic latencies Index. décimale : PER Périodiques Résumé : Previous research has shown that autistic individuals look at other people less and orient to them more slowly than others. Yet, it is still unclear if this represents general visual differences (e.g. slower looking at any new information, social or not) or a uniquely social difference (e.g. only slower looking to humans but not objects). Here, we aimed to examine how quickly autistic and non-autistic adults look to and away from social (i.e. faces) and non-social information (i.e. squares and houses). We used an attentional shifting task with two images where sometimes the first image disappears before the new image appears (makes it easier to notice the new image) and other times it stays on the screen when the new image appears. In Experiment 1, we showed schematic faces and squares to 27 autistic and 26 non-autistic adults, and in Experiment 2, we showed photographs of faces and houses to 18 autistic and 17 non-autistic adults. In general, autistic adults looked at the new non-social or social images similarly to non-autistic adults. Yet, only autistic adults looked at new social information faster when the first image disappeared before the new image appeared. This shows that autistic individuals may find it easier to notice new social information if their attention is not already occupied. En ligne : http://dx.doi.org/10.1177/13623613211001619 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=484 [article] Attentional shifting differences in autism: Domain general, domain specific or both? [texte imprimé] / Simona SKRIPKAUSKAITE, Auteur ; Lance SLADE, Auteur ; Jennifer L. MAYER, Auteur . - p.1721-1733. Langues : Anglais (eng) in Autism > 26-6 (August 2022) . - p.1721-1733 Mots-clés : Adult  Attention  Autism Spectrum Disorder  Autistic Disorder  Humans  adults  autism  eye tracking  gap–overlap  saccadic latencies Index. décimale : PER Périodiques Résumé : Previous research has shown that autistic individuals look at other people less and orient to them more slowly than others. Yet, it is still unclear if this represents general visual differences (e.g. slower looking at any new information, social or not) or a uniquely social difference (e.g. only slower looking to humans but not objects). Here, we aimed to examine how quickly autistic and non-autistic adults look to and away from social (i.e. faces) and non-social information (i.e. squares and houses). We used an attentional shifting task with two images where sometimes the first image disappears before the new image appears (makes it easier to notice the new image) and other times it stays on the screen when the new image appears. In Experiment 1, we showed schematic faces and squares to 27 autistic and 26 non-autistic adults, and in Experiment 2, we showed photographs of faces and houses to 18 autistic and 17 non-autistic adults. In general, autistic adults looked at the new non-social or social images similarly to non-autistic adults. Yet, only autistic adults looked at new social information faster when the first image disappeared before the new image appeared. This shows that autistic individuals may find it easier to notice new social information if their attention is not already occupied. En ligne : http://dx.doi.org/10.1177/13623613211001619 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=484

Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons / Qiong XU in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 65 p. Titre : Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons Type de document : texte imprimé Auteurs : Qiong XU, Auteur ; Yuan-Yuan LIU, Auteur ; Xiaoming WANG, Auteur ; Guo-he TAN, Auteur ; Hui-Ping LI, Auteur ; Samuel W. HULBERT, Auteur ; Chun-Yang LI, Auteur ; Chun-Chun HU, Auteur ; Z.Q. XIONG, Auteur ; Xiu XU, Auteur ; Yong-hui JIANG, Auteur Article en page(s) : 65 p. Langues : Anglais (eng) Mots-clés : Animals  Autistic Disorder/*genetics/pathology  Cells, Cultured  Cerebral Cortex/cytology/growth & development  DNA-Binding Proteins/*genetics/metabolism  Humans  Mice  Mice, Inbred C57BL  *Neurogenesis  Neurons/cytology/*metabolism/physiology  *Autism spectrum disorder (ASD)  *chd8  *Chromatin remodeling  *Neurite growth  *Neurodevelopment  Animal Care and Use Committee-approved protocols both at Children's Hospital of  Fudan University ethics approval ID: 2015-87 and Duke University. Human  postmortem brain tissues: The use of archived human postmortem brain tissues is  approved by Institute Review Board at Duke University.Not applicableThe authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: Mutations in CHD8, chromodomain helicase DNA-binding protein 8, are among the most replicated and common findings in genetic studies of autism spectrum disorder (ASD). The CHD8 protein is believed to act as a transcriptional regulator by remodeling chromatin structure and recruiting histone H1 to target genes. The mechanism by which deficiency of CHD8 causes ASD has not been fully elucidated. Methods: We examined the expression of CHD8 in human and mouse brains using both immunohistochemistry and RNA in situ hybridization. We performed in utero electroporation, neuronal culture, and biochemical analysis using RNAi to examine the functional consequences of CHD8 deficiency. Results: We discovered that CHD8 is expressed highly in neurons and at low levels in glia cells in both humans and mice. Specifically, CHD8 is localized predominately in the nucleus of both MAP2 and parvalbumin-positive neurons. In the developing mouse brain, expression of Chd8 peaks from E16 to E18 and then decreases significantly at P14 to adulthood. Knockdown of Chd8 results in reduced axon and dendritic growth, disruption of axon projections to the contralateral cortex, and delayed neuronal migration at E18.5 which recovers by P3 and P7. Conclusion: Our findings indicate an important role for CHD8 in dendritic and axon development and neuronal migration and thus offer novel insights to further dissect the underlying molecular and circuit mechanisms of ASD caused by CHD8 deficiency. En ligne : https://dx.doi.org/10.1186/s13229-018-0244-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Autism-associated CHD8 deficiency impairs axon development and migration of cortical neurons [texte imprimé] / Qiong XU, Auteur ; Yuan-Yuan LIU, Auteur ; Xiaoming WANG, Auteur ; Guo-he TAN, Auteur ; Hui-Ping LI, Auteur ; Samuel W. HULBERT, Auteur ; Chun-Yang LI, Auteur ; Chun-Chun HU, Auteur ; Z.Q. XIONG, Auteur ; Xiu XU, Auteur ; Yong-hui JIANG, Auteur . - 65 p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 65 p. Mots-clés : Animals  Autistic Disorder/*genetics/pathology  Cells, Cultured  Cerebral Cortex/cytology/growth & development  DNA-Binding Proteins/*genetics/metabolism  Humans  Mice  Mice, Inbred C57BL  *Neurogenesis  Neurons/cytology/*metabolism/physiology  *Autism spectrum disorder (ASD)  *chd8  *Chromatin remodeling  *Neurite growth  *Neurodevelopment  Animal Care and Use Committee-approved protocols both at Children's Hospital of  Fudan University ethics approval ID: 2015-87 and Duke University. Human  postmortem brain tissues: The use of archived human postmortem brain tissues is  approved by Institute Review Board at Duke University.Not applicableThe authors  declare that they have no competing interests.Springer Nature remains neutral  with regard to jurisdictional claims in published maps and institutional  affiliations. Index. décimale : PER Périodiques Résumé : Background: Mutations in CHD8, chromodomain helicase DNA-binding protein 8, are among the most replicated and common findings in genetic studies of autism spectrum disorder (ASD). The CHD8 protein is believed to act as a transcriptional regulator by remodeling chromatin structure and recruiting histone H1 to target genes. The mechanism by which deficiency of CHD8 causes ASD has not been fully elucidated. Methods: We examined the expression of CHD8 in human and mouse brains using both immunohistochemistry and RNA in situ hybridization. We performed in utero electroporation, neuronal culture, and biochemical analysis using RNAi to examine the functional consequences of CHD8 deficiency. Results: We discovered that CHD8 is expressed highly in neurons and at low levels in glia cells in both humans and mice. Specifically, CHD8 is localized predominately in the nucleus of both MAP2 and parvalbumin-positive neurons. In the developing mouse brain, expression of Chd8 peaks from E16 to E18 and then decreases significantly at P14 to adulthood. Knockdown of Chd8 results in reduced axon and dendritic growth, disruption of axon projections to the contralateral cortex, and delayed neuronal migration at E18.5 which recovers by P3 and P7. Conclusion: Our findings indicate an important role for CHD8 in dendritic and axon development and neuronal migration and thus offer novel insights to further dissect the underlying molecular and circuit mechanisms of ASD caused by CHD8 deficiency. En ligne : https://dx.doi.org/10.1186/s13229-018-0244-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome / Carrie R. JONAK in Journal of Neurodevelopmental Disorders, 14 (2022)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 14 (2022) Titre : Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome Type de document : texte imprimé Auteurs : Carrie R. JONAK, Auteur ; Ernest V. PEDAPATI, Auteur ; Lauren M. SCHMITT, Auteur ; Samantha A. ASSAD, Auteur ; Manbir S. SANDHU, Auteur ; Lisa DESTEFANO, Auteur ; Lauren ETHRIDGE, Auteur ; Khaleel A. RAZAK, Auteur ; John A. SWEENEY, Auteur ; Devin K. BINDER, Auteur ; Craig A. ERICKSON, Auteur Langues : Anglais (eng) Mots-clés : Animals  Baclofen/pharmacology  Disease Models, Animal  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/drug therapy  Humans  Male  Mice  Mice, Knockout  Autism  Baclofen  Biomarker  Electroencephalography  Fragile X syndrome  Multielectrode array  in fragile X syndrome held by the Cincinnati Children’s Research Foundation  (CCRF) and licensed out at the discretion of CCRF. CAE is a current consultant to  Impel, Stalicla, and Scioto Bioscience. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. METHODS: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABA(B) selective agonist racemic baclofen (RBAC). RESULTS: In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. CONCLUSIONS: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. TRIAL REGISTRATION: The human experiments are registered under NCT02998151. En ligne : https://dx.doi.org/10.1186/s11689-022-09455-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574 [article] Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome [texte imprimé] / Carrie R. JONAK, Auteur ; Ernest V. PEDAPATI, Auteur ; Lauren M. SCHMITT, Auteur ; Samantha A. ASSAD, Auteur ; Manbir S. SANDHU, Auteur ; Lisa DESTEFANO, Auteur ; Lauren ETHRIDGE, Auteur ; Khaleel A. RAZAK, Auteur ; John A. SWEENEY, Auteur ; Devin K. BINDER, Auteur ; Craig A. ERICKSON, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 14 (2022) Mots-clés : Animals  Baclofen/pharmacology  Disease Models, Animal  Fragile X Mental Retardation Protein/genetics  Fragile X Syndrome/complications/drug therapy  Humans  Male  Mice  Mice, Knockout  Autism  Baclofen  Biomarker  Electroencephalography  Fragile X syndrome  Multielectrode array  in fragile X syndrome held by the Cincinnati Children’s Research Foundation  (CCRF) and licensed out at the discretion of CCRF. CAE is a current consultant to  Impel, Stalicla, and Scioto Bioscience. Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. METHODS: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABA(B) selective agonist racemic baclofen (RBAC). RESULTS: In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. CONCLUSIONS: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. TRIAL REGISTRATION: The human experiments are registered under NCT02998151. En ligne : https://dx.doi.org/10.1186/s11689-022-09455-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=574

Brief Report: Preferred Processing of Social Stimuli in Autism: A Perception Task / A. MEERMEIER in Journal of Autism and Developmental Disorders, 52-7 (July 2022)  

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Closing the species gap: Translational approaches to studying sensory processing differences relevant for autism spectrum disorder / Kaela E. SCOTT in Autism Research, 14-7 (July 2021)  

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Culture and psychopathology: An attempt at reconsidering the role of social learning / Peter FONAGY in Development and Psychopathology, 34-4 (October 2022)  

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Developmental delays in cortical auditory temporal processing in a mouse model of Fragile X syndrome / Katilynne CROOM in Journal of Neurodevelopmental Disorders, 15 (2023)  

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Developmental studies in fragile X syndrome / Khaleel A. RAZAK in Journal of Neurodevelopmental Disorders, 12 (2020)  

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