Astrocytes Prevent Abnormal Neuronal Development in the Fragile X Mouse Journal Articles

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.

authors

• Jacobs, Shelley
• Doering, Laurie Caley

status

• published 

publication date

• March 24, 2010

has subject area

• 11 Medical and Health Sciences (FoR)
• 17 Psychology and Cognitive Sciences (FoR)
• Animals (MeSH)
• Animals, Newborn (MeSH)
• Astrocytes (MeSH)
• Coculture Techniques (MeSH)
• Dendrites (MeSH)
• Disease Models, Animal (MeSH)
• Disks Large Homolog 4 Protein (MeSH)
• Embryo, Mammalian (MeSH)
• Fragile X Mental Retardation Protein (MeSH)
• Fragile X Syndrome (MeSH)
• Gene Expression Regulation, Developmental (MeSH)
• Guanylate Kinases (MeSH)
• Hippocampus (MeSH)
• Intracellular Signaling Peptides and Proteins (MeSH)
• Membrane Proteins (MeSH)
• Mice (MeSH)
• Mice, Transgenic (MeSH)
• Microtubule-Associated Proteins (MeSH)
• Mutation (MeSH)
• Neurology & Neurosurgery (Science Metrix)
• Neurons (MeSH)
• Statistics, Nonparametric (MeSH)
• Synaptophysin (MeSH)

published in

• Journal of Neuroscience  Journal

keywords

• Animals
• Animals, Newborn
• Astrocytes
• Coculture Techniques
• Dendrites
• Disease Models, Animal
• Disks Large Homolog 4 Protein
• Embryo, Mammalian
• Fragile X Mental Retardation Protein
• Fragile X Syndrome
• Gene Expression Regulation, Developmental
• Guanylate Kinases
• Hippocampus
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• Mice
• Mice, Transgenic
• Microtubule-Associated Proteins
• Mutation
• Neurons
• Statistics, Nonparametric
• Synaptophysin

Digital Object Identifier (DOI)

• 10.1523/jneurosci.5027-09.2010

start page

• 4508

end page

• 4514

volume

• 30

issue

• 12