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Astrocyte glypican 5 regulates synapse maturation and stabilization
Alexandra P Bosworth, Minerva Contreras, Laura Sancho, Isabel H. Salas, Adrien Paumier, Sammy Weiser Novak, Uri Manor, Nicola J. Allen. Cell Reports, 2025-03-01
Topic: Brain proteins, microglia and lab models
The maturation and stabilization of appropriate synaptic connections is a vital step in neural circuit development; however, the molecular signals underlying these processes are not fully understood. We show that astrocytes, through production of glypican 5 (GPC5), are required for maturation and refinement of synapses in the mouse cortex during the critical period. In the absence of astrocyte GPC5, thalamocortical synapses show structural immaturity, including smaller presynaptic terminals, decreased postsynaptic density area, and presence of more postsynaptic partners at multisynaptic connections. This structural immaturity is accompanied by a delay in developmental incorporation of GLUA2-containing AMPARs at intracortical synapses. The functional impact of this is that mice lacking astrocyte GPC5 exhibit increased levels of ocular dominance plasticity in adulthood. This demonstrates that astrocyte GPC5 is necessary for maturation and stabilization of synaptic connections, which has implications for disorders with altered synaptic function where GPC5 levels are altered, including Alzheimer's disease and frontotemporal dementia.
Key findings
- We show that astrocytes, through production of glypican 5 (GPC5), are required for maturation and refinement of synapses in the mouse cortex during the critical period.
- In the absence of astrocyte GPC5, thalamocortical synapses show structural immaturity, including smaller presynaptic terminals, decreased postsynaptic density area, and presence of more postsynaptic partners at multisynaptic connections.
- This structural immaturity is accompanied by a delay in developmental incorporation of GLUA2-containing AMPARs at intracortical synapses.
- The functional impact of this is that mice lacking astrocyte GPC5 exhibit increased levels of ocular dominance plasticity in adulthood.
- This demonstrates that astrocyte GPC5 is necessary for maturation and stabilization of synaptic connections, which has implications for disorders with altered synaptic function where GPC5 levels are altered, including Alzheimer's disease and frontotemporal dementia.
Why it matters
In mice, astrocyte glypican 5 was required for normal synapse maturation and stabilization, and its absence caused structural and functional changes in brain connections. The authors note implications for disorders with altered synaptic function including Alzheimer's disease, but this is animal work and does not show a treatment.
Study details
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cell Reports) |
| Journal's citation record | 3 / 4 | Cell Reports: journal h-index 321 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 28 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 9.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 28 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Nicola J. Allen: h-index 36 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of California San Diego: institution h-index 1,852 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40048429) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Bosworth, A. P., Contreras, M., Sancho, L., Salas, I. H., Paumier, A., Novak, S. W., et al. (2025). Astrocyte glypican 5 regulates synapse maturation and stabilization. Cell Reports. https://doi.org/10.1016/j.celrep.2025.115374
Vancouver
Bosworth AP, Contreras M, Sancho L, Salas IH, Paumier A, Novak SW, et al. Astrocyte glypican 5 regulates synapse maturation and stabilization. Cell Reports. 2025. doi:10.1016/j.celrep.2025.115374. PMID: 40048429.
BibTeX
@article{bosworth2025-40048429,
author = {Bosworth, Alexandra P and Contreras, Minerva and Sancho, Laura and Salas, Isabel H. and Paumier, Adrien and Novak, Sammy Weiser and Manor, Uri and Allen, Nicola J.},
title = {{Astrocyte glypican 5 regulates synapse maturation and stabilization}},
journal = {Cell Reports},
year = {2025},
doi = {10.1016/j.celrep.2025.115374},
pmid = {40048429},
url = {https://doi.org/10.1016/j.celrep.2025.115374}
}
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