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Non–cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology

Nature Neuroscience volume 12, pages 311317 (2009) | Download Citation

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Abstract

The neurodevelopmental disorder Rett syndrome (RTT) is caused by sporadic mutations in the transcriptional factor methyl-CpG–binding protein 2 (MeCP2). Although it is thought that the primary cause of RTT is cell autonomous, resulting from a lack of functional MeCP2 in neurons, whether non–cell autonomous factors contribute to the disease is unknown. We found that the loss of MeCP2 occurs not only in neurons but also in glial cells of RTT brains. Using an in vitro co-culture system, we found that mutant astrocytes from a RTT mouse model, and their conditioned medium, failed to support normal dendritic morphology of either wild-type or mutant hippocampal neurons. Our studies suggest that astrocytes in the RTT brain carrying MeCP2 mutations have a non–cell autonomous effect on neuronal properties, probably as a result of aberrant secretion of soluble factor(s).

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Acknowledgements

The authors thank J. Levine and L. Evans for providing the enriched glial cultures for the initial immunostaining analysis; P. Brehm, R. Goodman, T. Reese and G. Banker for valuable discussions about the results; and D.D. Lu and R. Spektor for technical assistance. This work was supported in part by a grant from the International Rett Syndrome Foundation to N.B. and a US National Institutes of Health grant to G.M. and N.B. G.M. is an Investigator of the Howard Hughes Medical Institute.

Author information

Author notes

    • Daniel T Lioy
    •  & Christopher Grunseich

    These authors contributed equally to this work.

Affiliations

  1. Howard Hughes Medical Institute, Department of Neurobiology and Behavior, State University of New York, Stony Brook, New York 11794, USA.

    • Nurit Ballas
    • , Christopher Grunseich
    •  & Gail Mandel
  2. Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, New York 11794-5215, USA.

    • Nurit Ballas
  3. Vollum Institute and Howard Hughes Medical Institute, Oregon Health and Science University, Portland, Oregon 97239, USA.

    • Daniel T Lioy
    •  & Gail Mandel

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Contributions

N.B., D.T.L., C.G. and G.M. designed the experiments. N.B., D.T.L. and C.G. carried out the experiments. N.B., D.T.L. and G.M. wrote the paper. N.B. and G.M. supervised the project.

Corresponding author

Correspondence to Nurit Ballas.

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DOI

https://doi.org/10.1038/nn.2275

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