Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders / Jordan M. RAMSEY in Molecular Autism, (August 2013)  

Public ISBD [article]  inMolecular Autism > (August 2013) . - 18 p. Titre : Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Jordan M. RAMSEY, Auteur ; Paul C. GUEST, Auteur ; Jantine A.C. BROEK, Auteur ; Jeffrey GLENNON, Auteur ; Nanda N. ROMMELSE, Auteur ; Barbara FRANKE, Auteur ; Hassan RAHMOUNE, Auteur ; Jan K. BUITELAAR, Auteur ; Sabine BAHN, Auteur Année de publication : 2013 Article en page(s) : 18 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood and adolescent development. Methods We carried out a multiplex immunoassay profiling analysis of serum samples from 37 individuals with a diagnosis of ASD and their matched, non-affected siblings, aged between 4 and 18 years, to identify molecular pathways affected over the course of ASDs. Results This analysis revealed age-dependent differences in the levels of 12 proteins involved in inflammation, growth and hormonal signaling. Conclusions These deviations in age-related molecular trajectories provide further insight into the progression and pathophysiology of the disorder and, if replicated, may contribute to better classification of ASD individuals, as well as to improved treatment and prognosis. The results also underline the importance of stratifying and analyzing samples by age, especially in ASD and potentially other developmental disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-4-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Identification of an age-dependent biomarker signature in children and adolescents with autism spectrum disorders [Texte imprimé et/ou numérique] / Jordan M. RAMSEY, Auteur ; Paul C. GUEST, Auteur ; Jantine A.C. BROEK, Auteur ; Jeffrey GLENNON, Auteur ; Nanda N. ROMMELSE, Auteur ; Barbara FRANKE, Auteur ; Hassan RAHMOUNE, Auteur ; Jan K. BUITELAAR, Auteur ; Sabine BAHN, Auteur . - 2013 . - 18 p. Langues : Anglais (eng) in Molecular Autism > (August 2013) . - 18 p. Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASDs) are neurodevelopmental conditions with symptoms manifesting before the age of 3, generally persisting throughout life and affecting social development and communication. Here, we have investigated changes in protein biomarkers in blood during childhood and adolescent development. Methods We carried out a multiplex immunoassay profiling analysis of serum samples from 37 individuals with a diagnosis of ASD and their matched, non-affected siblings, aged between 4 and 18 years, to identify molecular pathways affected over the course of ASDs. Results This analysis revealed age-dependent differences in the levels of 12 proteins involved in inflammation, growth and hormonal signaling. Conclusions These deviations in age-related molecular trajectories provide further insight into the progression and pathophysiology of the disorder and, if replicated, may contribute to better classification of ASD individuals, as well as to improved treatment and prognosis. The results also underline the importance of stratifying and analyzing samples by age, especially in ASD and potentially other developmental disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-4-27 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Proteomic analysis of post mortem brain tissue from autism patients: evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity-related proteins / Jantine A.C. BROEK in Molecular Autism, (July 2014)  

Public ISBD [article]  inMolecular Autism > (July 2014) . - p.1-8 Titre : Proteomic analysis of post mortem brain tissue from autism patients: evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity-related proteins Type de document : Texte imprimé et/ou numérique Auteurs : Jantine A.C. BROEK, Auteur ; Paul C. GUEST, Auteur ; Hassan RAHMOUNE, Auteur ; Sabine BAHN, Auteur Article en page(s) : p.1-8 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism is a neurodevelopmental disorder characterized by impaired language, communication and social skills. Although genetic studies have been carried out in this field, none of the genes identified have led to an explanation of the underlying causes. Here, we have investigated molecular alterations by proteomic profiling of post mortem brain samples from autism patients and controls. The analysis focussed on prefrontal cortex and cerebellum as previous studies have found that these two brain regions are structurally and functionally connected, and they have been implicated in autism. En ligne : http://dx.doi.org/10.1186/2040-2392-5-41 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] Proteomic analysis of post mortem brain tissue from autism patients: evidence for opposite changes in prefrontal cortex and cerebellum in synaptic connectivity-related proteins [Texte imprimé et/ou numérique] / Jantine A.C. BROEK, Auteur ; Paul C. GUEST, Auteur ; Hassan RAHMOUNE, Auteur ; Sabine BAHN, Auteur . - p.1-8. Langues : Anglais (eng) in Molecular Autism > (July 2014) . - p.1-8 Index. décimale : PER Périodiques Résumé : Autism is a neurodevelopmental disorder characterized by impaired language, communication and social skills. Although genetic studies have been carried out in this field, none of the genes identified have led to an explanation of the underlying causes. Here, we have investigated molecular alterations by proteomic profiling of post mortem brain samples from autism patients and controls. The analysis focussed on prefrontal cortex and cerebellum as previous studies have found that these two brain regions are structurally and functionally connected, and they have been implicated in autism. En ligne : http://dx.doi.org/10.1186/2040-2392-5-41 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

Synaptic vesicle dynamic changes in a model of fragile X / Jantine A.C. BROEK in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 17p. Titre : Synaptic vesicle dynamic changes in a model of fragile X Type de document : Texte imprimé et/ou numérique Auteurs : Jantine A.C. BROEK, Auteur ; Z. LIN, Auteur ; H. M. DE GRUITER, Auteur ; H. VAN 'T SPIJKER, Auteur ; E. D. HAASDIJK, Auteur ; David COX, Auteur ; S. OZCAN, Auteur ; G. W. A. VAN CAPPELLEN, Auteur ; A. B. HOUTSMULLER, Auteur ; R. WILLEMSEN, Auteur ; C. I. DE ZEEUW, Auteur ; S. BAHN, Auteur Article en page(s) : 17p. Langues : Anglais (eng) Mots-clés : Animals  Animals, Congenic  Cells, Cultured  Cerebellum/pathology/physiopathology  Fluorescent Dyes  Fragile X Mental Retardation Protein/genetics/physiology  Fragile X Syndrome/genetics/metabolism/physiopathology  Hippocampus/pathology/physiopathology  Intravital Microscopy  Male  Mass Spectrometry/methods  Mice  Mice, Inbred C57BL  Mice, Knockout  Mice, Neurologic Mutants  Microscopy, Electron  Models, Animal  Nerve Tissue Proteins/analysis  Presynaptic Terminals/secretion  Proteome  Purkinje Cells/physiology/ultrastructure  Pyridinium Compounds  Quaternary Ammonium Compounds  Signal Transduction  Synaptic Transmission  Synaptic Vesicles/metabolism  Synaptosomes/metabolism  Electron microscopy  Fragile X syndrome (FXS)  Mass spectrometry (MS)  Quantitative live-cell imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. METHODS: Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. RESULTS: Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. CONCLUSIONS: Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS. En ligne : http://dx.doi.org/10.1186/s13229-016-0080-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Synaptic vesicle dynamic changes in a model of fragile X [Texte imprimé et/ou numérique] / Jantine A.C. BROEK, Auteur ; Z. LIN, Auteur ; H. M. DE GRUITER, Auteur ; H. VAN 'T SPIJKER, Auteur ; E. D. HAASDIJK, Auteur ; David COX, Auteur ; S. OZCAN, Auteur ; G. W. A. VAN CAPPELLEN, Auteur ; A. B. HOUTSMULLER, Auteur ; R. WILLEMSEN, Auteur ; C. I. DE ZEEUW, Auteur ; S. BAHN, Auteur . - 17p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 17p. Mots-clés : Animals  Animals, Congenic  Cells, Cultured  Cerebellum/pathology/physiopathology  Fluorescent Dyes  Fragile X Mental Retardation Protein/genetics/physiology  Fragile X Syndrome/genetics/metabolism/physiopathology  Hippocampus/pathology/physiopathology  Intravital Microscopy  Male  Mass Spectrometry/methods  Mice  Mice, Inbred C57BL  Mice, Knockout  Mice, Neurologic Mutants  Microscopy, Electron  Models, Animal  Nerve Tissue Proteins/analysis  Presynaptic Terminals/secretion  Proteome  Purkinje Cells/physiology/ultrastructure  Pyridinium Compounds  Quaternary Ammonium Compounds  Signal Transduction  Synaptic Transmission  Synaptic Vesicles/metabolism  Synaptosomes/metabolism  Electron microscopy  Fragile X syndrome (FXS)  Mass spectrometry (MS)  Quantitative live-cell imaging Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder that is the most common heritable cause of intellectual disability and the most frequent monogenic cause of autism spectrum disorders (ASD). FXS is caused by an expansion of trinucleotide repeats in the promoter region of the fragile X mental retardation gene (Fmr1). This leads to a lack of fragile X mental retardation protein (FMRP), which regulates translation of a wide range of messenger RNAs (mRNAs). The extent of expression level alterations of synaptic proteins affected by FMRP loss and their consequences on synaptic dynamics in FXS has not been fully investigated. METHODS: Here, we used an Fmr1 knockout (KO) mouse model to investigate the molecular mechanisms underlying FXS by monitoring protein expression changes using shotgun label-free liquid-chromatography mass spectrometry (LC-MS(E)) in brain tissue and synaptosome fractions. FXS-associated candidate proteins were validated using selected reaction monitoring (SRM) in synaptosome fractions for targeted protein quantification. Furthermore, functional alterations in synaptic release and dynamics were evaluated using live-cell imaging, and interpretation of synaptic dynamics differences was investigated using electron microscopy. RESULTS: Key findings relate to altered levels of proteins involved in GABA-signalling, especially in the cerebellum. Further exploration using microscopy studies found reduced synaptic vesicle unloading of hippocampal neurons and increased vesicle unloading in cerebellar neurons, which suggests a general decrease of synaptic transmission. CONCLUSIONS: Our findings suggest that FMRP is a regulator of synaptic vesicle dynamics, which supports the role of FMRP in presynaptic functions. Taken together, these studies provide novel insights into the molecular changes associated with FXS. En ligne : http://dx.doi.org/10.1186/s13229-016-0080-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

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