Astrocytes prevent abnormal neuronal development in the fragile X mouse.
Open accessAbstract
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.
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FMRP-deficient astrocytes contribute to more complex dendritic arborisation when co-cultured with hippocampal neurons compared to co-culture with WT astrocytes.
“Co-culturing studies of Fmr1 KO astrocytes with hippocampal neurons have revealed that FMRP-deficient astrocytes contribute to more complex dendritic arborisation when compared to co-culture with WT astrocytes (Jacobs and Doering, 2010).”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Jacobs and Doering, 2010
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Research works printed but not linked: 1
- Jacob S, Doering LC (2009) Primary dissociated astrocyte and neuronal co- culture. In: Protocols for neural cell culture, Ed 4 (Doering LC, ed), pp. 269 -284. New York: Humana.
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“…activation, aberrant calcium signaling, disturbed glutamate uptake, downstream impacts on neurite outgrowth and synaptogenesis, and APOE secretion (Dong et al., 2018; Higashimori et al., 2016; Jacobs and Doering, 2010; Laurence and Fatemi, 2005; Trachtenberg et al., 2012; Vargas et al., 2005).”
Astrocytes in fragile X syndrome
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“Co-culturing studies of Fmr1 KO astrocytes with hippocampal neurons have revealed that FMRP-deficient astrocytes contribute to more complex dendritic arborisation when compared to co-culture with WT astrocytes (Jacobs and Doering, 2010).”
Reynolds, K. E., Huang, E., Sabbineni, M., Wiseman, E., Murtaza, N., Ahuja, D., Napier, M., Murphy, K. M., Singh, K. K., & Scott, A. L. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04181-w · Cited by 6 · see citing works
- Authors
- Jacobs, S., & Doering, L. C.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Doering, Laurie C.
- ORCID
- Jacobs, Shelley
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-03-24
- Volume
- 30
- Issue
- 12
- Pages
- 4508-4514
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6634485
- OpenAlex
- W2153646819
- Cited by
- 170
- References
- 6
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 11 · 2023: 4 · 2022: 10 · 2021: 9 · 2020: 10 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 19 · 2015: 13 · 2014: 19 · 2013: 11 · 2012: 12
- FWCI
- 7.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- 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
- astrocytes, fragile X syndrome, dendritic morphology, synaptic development, hippocampal neurons, neuronal development, astrocyte-neuron co-culture, neurodevelopmental disorders
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Animals, Newborn, Astrocytes, Dendrites, Disease Models, Animal, Embryo, Mammalian, Fragile X Syndrome, Hippocampus, Membrane Proteins, Mice, Transgenic, Microtubule-Associated Proteins, Mutation, Neurons, Synaptophysin, Gene Expression Regulation, Developmental, Statistics, Nonparametric, Coculture Techniques, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases, Fragile X Mental Retardation Protein, Fragile X Messenger Ribonucleoprotein 1
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