Abstract
Astrocytes are now distinguished as major regulators of neuronal growth and synaptic development. Recently, they have been identified as key players in the progression of a number of developmental disorders; however, in fragile X syndrome (FXS), the role of astrocytes is not known. Using a coculture design, we found that hippocampal neurons exhibited abnormal dendritic morphology and a decreased number of presynaptic and postsynaptic protein aggregates when they were grown on astrocytes from a fragile X mouse. Moreover, we found that normal astrocytes could prevent the development of abnormal dendrite morphology and preclude the reduction of presynaptic and postsynaptic protein clusters in neurons from a fragile X mouse. These experiments are the first to establish a role for astrocytes in the altered neurobiology of FXS. Our results support the notion that astrocytes contribute to abnormal dendrite morphology and the dysregulated synapse development in FXS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Astrocytes / physiology*
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Coculture Techniques / methods
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Dendrites / pathology
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Disease Models, Animal
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Disks Large Homolog 4 Protein
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Embryo, Mammalian
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Fragile X Mental Retardation Protein / genetics
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Fragile X Syndrome / pathology*
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Gene Expression Regulation, Developmental / physiology
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Guanylate Kinases
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Hippocampus / abnormalities*
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Hippocampus / pathology*
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / metabolism
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Mice
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Mice, Transgenic
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Microtubule-Associated Proteins / metabolism
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Mutation / genetics
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Neurons / pathology*
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Neurons / physiology
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Statistics, Nonparametric
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Synaptophysin / metabolism
Substances
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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Fmr1 protein, mouse
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Microtubule-Associated Proteins
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Mtap2 protein, mouse
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Synaptophysin
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Fragile X Mental Retardation Protein
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Guanylate Kinases