The Experts below are selected from a list of 1575 Experts worldwide ranked by ideXlab platform
Abbas F. Sadikot - One of the best experts on this subject based on the ideXlab platform.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington's disease.
Acta neuropathologica communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
Gabriel Crevier-sorbo - One of the best experts on this subject based on the ideXlab platform.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington's disease.
Acta neuropathologica communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
Raphael Crevier-sorbo - One of the best experts on this subject based on the ideXlab platform.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington's disease.
Acta neuropathologica communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
Vladimir V. Rymar - One of the best experts on this subject based on the ideXlab platform.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington’s disease
Acta Neuropathologica Communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
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Thalamostriatal degeneration contributes to dystonia and cholinergic interneuron dysfunction in a mouse model of Huntington's disease.
Acta neuropathologica communications, 2020Co-Authors: Gabriel Crevier-sorbo, Vladimir V. Rymar, Raphael Crevier-sorbo, Abbas F. SadikotAbstract:Huntington’s disease (HD) is an autosomal dominant Trinucleotide Repeat Disorder characterized by choreiform movements, dystonia and striatal neuronal loss. Amongst multiple cellular processes, abnormal neurotransmitter signalling and decreased trophic support from glutamatergic cortical afferents are major mechanisms underlying striatal degeneration. Recent work suggests that the thalamostriatal (TS) system, another major source of glutamatergic input, is abnormal in HD although its phenotypical significance is unknown. We hypothesized that TS dysfunction plays an important role in generating motor symptoms and contributes to degeneration of striatal neuronal subtypes. Our results using the R6/2 mouse model of HD indicate that neurons of the parafascicular nucleus (PF), the main source of TS afferents, degenerate at an early stage. PF lesions performed prior to motor dysfunction or striatal degeneration result in an accelerated dystonic phenotype and are associated with premature loss of cholinergic interneurons. The progressive loss of striatal medium spiny neurons and parvalbumin-positive interneurons observed in R6/2 mice is unaltered by PF lesions. Early striatal cholinergic ablation using a mitochondrial immunotoxin provides evidence for increased cholinergic vulnerability to cellular energy failure in R6/2 mice, and worsens the dystonic phenotype. The TS system therefore contributes to trophic support of striatal interneuron subtypes in the presence of neurodegenerative stress, and TS deafferentation may be a novel cell non-autonomous mechanism contributing to the pathogenesis of HD. Furthermore, behavioural experiments demonstrate that the TS system and striatal cholinergic interneurons are key motor-network structures involved in the pathogenesis of dystonia. This work suggests that treatments aimed at rescuing the TS system may preserve important elements of striatal structure and function and provide symptomatic relief in HD.
Flora Tassone - One of the best experts on this subject based on the ideXlab platform.
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Molecular Biomarkers in Fragile X Syndrome
Brain sciences, 2019Co-Authors: Marwa Zafarullah, Flora TassoneAbstract:Fragile X syndrome (FXS) is the most common inherited form of intellectual disability (ID) and a known monogenic cause of autism spectrum Disorder (ASD). It is a Trinucleotide Repeat Disorder, in which more than 200 CGG Repeats in the 5' untranslated region (UTR) of the fragile X mental retardation 1 (FMR1) gene causes methylation of the promoter with consequent silencing of the gene, ultimately leading to the loss of the encoded fragile X mental retardation 1 protein, FMRP. FMRP is an RNA binding protein that plays a primary role as a repressor of translation of various mRNAs, many of which are involved in the maintenance and development of neuronal synaptic function and plasticity. In addition to intellectual disability, patients with FXS face several behavioral challenges, including anxiety, hyperactivity, seizures, repetitive behavior, and problems with executive and language performance. Currently, there is no cure or approved medication for the treatment of the underlying causes of FXS, but in the past few years, our knowledge about the proteins and pathways that are dysregulated by the loss of FMRP has increased, leading to clinical trials and to the path of developing molecular biomarkers for identifying potential targets for therapies. In this paper, we review candidate molecular biomarkers that have been identified in preclinical studies in the FXS mouse animal model and are now under validation for human applications or have already made their way to clinical trials.
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Fragile X syndrome
Nature reviews. Disease primers, 2017Co-Authors: Randi J Hagerman, Flora Tassone, Elizabeth Berry-kravis, Heather Cody Hazlett, Donald B. Bailey, Hervé Moine, R. Frank Kooy, Ilse Gantois, Nahum Sonenberg, Jean-louis MandelAbstract:Fragile X syndrome (FXS) is the leading inherited form of intellectual disability and autism spectrum Disorder, and patients can present with severe behavioural alterations, including hyperactivity, impulsivity and anxiety, in addition to poor language development and seizures. FXS is a Trinucleotide Repeat Disorder, in which >200 Repeats of the CGG motif in FMR1 leads to silencing of the gene and the consequent loss of its product, fragile X mental retardation 1 protein (FMRP). FMRP has a central role in gene expression and regulates the translation of potentially hundreds of mRNAs, many of which are involved in the development and maintenance of neuronal synaptic connections. Indeed, disturbances in neuroplasticity is a key finding in FXS animal models, and an imbalance in inhibitory and excitatory neuronal circuits is believed to underlie many of the clinical manifestations of this Disorder. Our knowledge of the proteins that are regulated by FMRP is rapidly growing, and this has led to the identification of multiple targets for therapeutic intervention, some of which have already moved into clinical trials or clinical practice.
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Molecular Diagnostics and Genetic Counseling in Fragile X Syndrome and FMR1-Associated Disorders
Fragile X Syndrome, 2017Co-Authors: Flora Tassone, Montserrat MilàAbstract:Abstract Fragile X syndrome (FXS) is a CGG Trinucleotide–Repeat Disorder and the most common heritable form of intellectually disability and autism. The gold standard diagnosis for FXS uses a combination of Southern blot and PCR analysis. However, in the past few years, several robust PCR-based methodologies, able to amplify expanded alleles even in the full mutation range, with or without methylation, have been developed. In this chapter, we review the usage and application of these methodologies in different settings. Further, we discuss genetic counseling of alleles throughout the range (normal to full mutation) in both males and females.
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Advanced technologies for the molecular diagnosis of fragile X syndrome
Expert review of molecular diagnostics, 2015Co-Authors: Flora TassoneAbstract:Fragile X syndrome (FXS), a Trinucleotide Repeat Disorder, is the most common heritable form of cognitive impairment. Since the discovery of the FMR1 gene in 1991, great strides have been made in the field of molecular diagnosis for FXS. Cytogenetic analysis, which was the method of diagnosis in the early 1990, was replaced by Southern blot and PCR analysis albeit with some limitations. In the past few years many PCR-based methodologies, able to amplify large full mutation expanded alleles, with or without methylation, have been proposed. Reviewed here are the advantages, disadvantages and limitations of the most recent developments in the field of FXS diagnosis.
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Expression of the FMR1 gene
Cytogenetic and Genome Research, 2003Co-Authors: Flora Tassone, Paul J. HagermanAbstract:Fragile X syndrome is a Trinucleotide Repeat Disorder in which a (CGG)n element located within the 5′ untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene expands to more t
