Altered developmental expression of the astrocyte-secreted factors hevin and SPARC in the fragile X mouse model.
Open accessAbstract
Astrocyte dysfunction has been indicated in many neurodevelopmental disorders, including Fragile X Syndrome (FXS). FXS is caused by a deficiency in fragile X mental retardation protein (FMRP). FMRP regulates the translation of numerous mRNAs and its loss disturbs the composition of proteins important for dendritic spine and synapse development. Here, we investigated whether the astrocyte-derived factors hevin and SPARC, known to regulate excitatory synapse development, have altered expression in FXS. Specifically, we analyzed the expression of these factors in wild-type (WT) mice and in Fmr1 knock-out (KO) mice that lack FMRP expression. Samples were collected from the developing cortex and hippocampus (regions of dendritic spine abnormalities in FXS) of Fmr1 KO and WT pups. Hevin and SPARC showed altered expression patterns in Fmr1 KO mice compared to WT, in a brain-region specific manner. In cortical tissue, we found a transient increase in the level of hevin in postnatal day (P)14 Fmr1 KO mice, compared to WT. Additionally, there were modest decreases in Fmr1 KO cortical levels of SPARC at P7 and P14. In the hippocampus, hevin expression was much lower in P7 Fmr1 KO mice than in WT. At P14, hippocampal hevin levels were similar between genotypes, and by P21 Fmr1 KO hevin expression surpassed WT levels. These findings imply aberrant astrocyte signalling in FXS and suggest that the altered expression of hevin and SPARC contributes to abnormal synaptic development in FXS.
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Expression of SPARC is reduced in the cortex and hippocampus of the Fmr1 KO mouse.
“Conversely, expression of SPARC that inhibits the synaptogenic function of hevin and negatively regulates the formation of excitatory synapses (Risher et al., 2014) is reduced in the cortex and hippocampus of the Fmr1 KO mouse (Wallingford et al., 2017).”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Wallingford et al., 2017
The Results section reports approximately 15% lower cortical SPARC levels in Fmr1 KO mice at P7 and P14, but no significant cortical difference at P21. In “Hevin Protein Levels, but Not SPARC Levels, Are Altered in the Hippocampus,” the authors report no significant hippocampal SPARC difference at P7, P14, or P21. The claim is therefore supported for the developing cortex at two time points, not for the hippocampus. (LLM, conf=0.92)
Experimental — accuracy not yet measuredCortical expression of hevin is increased in P14 Fmr1 KO mice compared with WT controls, consistent with an increase in density of thalamocortical synapses when WT neurons are cultured with Fmr1 KO astrocytes.
“Also, cortical expression of hevin that is necessary for the formation of thalamocortical excitatory synapses (Kucukdereli et al., 2011; Risher et al., 2014) is increased in P14 Fmr1 KO mice compared with WT controls consistent with an increase in the density of thalamocortical synapses when WT neurons are cultured with Fmr1 KO astrocytes (Wallingford et al., 2017).”
From Astrocytes in fragile X syndrome (2024) · cites this paper as Wallingford et al., 2017
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Self-citation
- Authors
- Wallingford, J., Scott, A. L., Rodrigues, K., & Doering, L. C.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Doering, Laurie C.
- ORCID
- Scott, Angela L.
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2017-08-29
- Volume
- 10
- Pages
- 268-268
- ISSN
- 1662-5099 (ISSN-L)
- PMC
- PMC5581809
- OpenAlex
- W2745685952
- Cited by
- 38
- References
- 52
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 8 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 4
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Molecular Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- FRAXA Research Foundation
- Fondation Brain 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 › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- fragile X syndrome, hevin, SPARC, FMRP, Fmr1 knockout mice, astrocytes, dendritic spine development, hippocampus, cerebral cortex, postnatal development, neurodevelopmental disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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