ArticleFrontiers in cellular neuroscience2016
Immature Responses to GABA in Fragile X Neurons Derived from Human Embryonic Stem Cells.
Article in Frontiers in cellular neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Elevated levels of FMRP-target MAP1B impair human and mouse neuronal development and mouse social behaviors via autophagy pathway.Nature communications · 2023Article
- Review
- Transcriptomic Analysis of Human Fragile X Syndrome Neurons Reveals Neurite Outgrowth Modulation by the TGFβ/BMP Pathway.International journal of molecular sciences · 2022Article
- Isoflurane inhibition of endocytosis is an anesthetic mechanism of action.Current biology : CB · 2022Article
- Mechanisms Driving the Emergence of Neuronal Hyperexcitability in Fragile X Syndrome.International journal of molecular sciences · 2022Review
- Article
- Decreased reproducibility and abnormal experience-dependent plasticity of network dynamics in Fragile X circuits.Scientific reports · 2020Article
- Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns.Molecular autism · 2020Article
- Partial FMRP expression is sufficient to normalize neuronal hyperactivity in Fragile X neurons.The European journal of neuroscience · 2020Article
- Molecular Biomarkers in Fragile X Syndrome.Brain sciences · 2019Review
- Modelling Protein Synthesis as A Biomarker in Fragile X Syndrome Patient-Derived Cells.Brain sciences · 2019Review
- Reduced mitochondrial fusion and Huntingtin levels contribute to impaired dendritic maturation and behavioral deficits in Fmr1-mutant mice.Nature neuroscience · 2019Article
- Molecular Mechanisms of Synaptic Dysregulation in Fragile X Syndrome and Autism Spectrum Disorders.Frontiers in molecular neuroscience · 2019Review
- Human Models Are Needed for Studying Human Neurodevelopmental Disorders.American journal of human genetics · 2018Review
- Aberrant RNA translation in fragile X syndrome: From FMRP mechanisms to emerging therapeutic strategies.Brain research · 2018Review
- The fragile X mutation impairs homeostatic plasticity in human neurons by blocking synaptic retinoic acid signaling.Science translational medicine · 2018Article
- Uncovering True Cellular Phenotypes: Using Induced Pluripotent Stem Cell-Derived Neurons to Study Early Insults in Neurodevelopmental Disorders.Frontiers in neurology · 2018Review
- Combination Therapy in Fragile X Syndrome; Possibilities and Pitfalls Illustrated by Targeting the mGluR5 and GABA Pathway Simultaneously.Frontiers in molecular neuroscience · 2017Article
- Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fragile X Syndrome (FXS) is the most common form of inherited cognitive disability. However, functional deficiencies in FX neurons have been described so far almost exclusively in animal models. In a recent study we found several functional deficits in FX neurons differentiated in-vitro from human embryonic stem cells (hESCs), including their inability to fire repetitive action potentials, and their lack of synaptic activity. Here, we investigated the responses of such neurons to pulse application of the neurotransmitter GABA. We found two distinct types of responses to GABA and sensitivity to the GABA-A receptor antagonist bicuculline; type 1 (mature) characterized by non-desensitized responses to GABA as well as a high sensitivity to bicuculline, and type 2 (immature) which are desensitized to GABA and insensitive to bicuculline. Type 1 responses were age-dependent and dominant in mature WT neurons. In contrast, FX neurons expressed primarily type 2 phenotype. Expression analysis of GABA-A receptor subunits demonstrated that this bias in human FX neurons was associated with a significant alteration in the expression pattern of the GABA-A receptor subunits α2 and β2. Our results indicate that FMRP may play a role in the development of the GABAergic synapse during neurogenesis. This is the first demonstration of the lack of a mature response to GABA in human FX neurons and may explain the inappropriate synaptic functions in FXS.
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