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Cited by 466Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

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

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Ballas, Nurit, Lioy, Daniel T, Grunseich, Christopher, Mandel, Gail·2009·Nature Neuroscience
DOI 10.1038/nn.2275PMC PMC3134296
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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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  • Wild-type neurons have abnormal dendritic morphology when co-cultured with MeCP2-deficient astrocytes, yet MeCP2-deficient neurons have normal dendritic morphology when co-cultured with wild-type astrocytes.

    “Interestingly, wild-type neurons have abnormal dendritic morphology when co-cultured with MeCP2-deficient astrocytes, yet MeCP2-deficient neurons have normal dendritic morphology when co-cultured with wild-type astrocytes [192].”

    From Rett syndrome: a neurological disorder with metabolic components (2018) · cites this paper as [192]

    The Results section (“RTT astrocytes cannot support normal neuronal growth”; page unavailable) reports abnormal dendritic morphology in wild-type neurons co-cultured with MeCP2-deficient astrocytes. The Results section (“RTT ACM cannot support normal neuronal growth”; page unavailable) also reports normal morphology in MeCP2-null neurons exposed to conditioned medium from wild-type astrocytes, but does not establish that result for co-culture with the astrocytes themselves. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • MECP2 mutant astrocytes contribute to neuronal alterations through non-cell-autonomous mechanisms.

    “and MECP2 mutant astrocytes contribute to neuronal alterations through non-cell-autonomous mechanisms (Albizzati et al., 2024;Ballas et al., 2009;Sun et al., 2023;Williams et al., 2014).”

    From Impaired astrocyte-to-neuron cholesterol trafficking drives synaptic dysfunction in Rett syndrome (2026) · cites this paper as Ballas et al., 2009

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Research works printed but not linked: 43

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Cited by

Sorted by citations

Authors
Ballas, N., Lioy, D. T., Grunseich, C., & Mandel, G.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Ballas, Nurit
ORCID
Venue
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Published
2009-02-22
Volume
12
Issue
3
Pages
311-317
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
DOI
10.1038/nn.2275
PMC
PMC3134296
OpenAlex
W1994974752
Cited by
466
References
7
Citations by year
2026: 13 · 2025: 12 · 2024: 15 · 2023: 11 · 2022: 24 · 2021: 27 · 2020: 16 · 2019: 13 · 2018: 24 · 2017: 26 · 2016: 39 · 2015: 45 · 2014: 27 · 2013: 42 · 2012: 52
FWCI
25.74
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD056503)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Rett syndrome, MeCP2, astrocytes, glial cells, dendritic morphology, non-cell-autonomous effects, hippocampal neurons, astrocyte-neuron co-culture, conditioned medium, soluble factors, neurodevelopmental disorders
MeSH terms
Animals, Dendrites, Male, Mice, Mutant Strains, Neuroglia, Neurons, Rett Syndrome, Coculture Techniques, Mice, Rats, Methyl-CpG-Binding Protein 2

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