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Neurotoxic reactive astrocytes are induced by activated microglia
Shane A. Liddelow, Kevin A. Guttenplan, Laura E. Clarke, F. Chris Bennett, Christopher J. Bohlen, Lucas Schirmer, Mariko L. Bennett, Alexandra E. Münch et al.. Nature, 2017-01-01
Topic: Brain proteins, microglia and lab models
This study investigated a subtype of reactive astrocytes called A1 and discovered that they are induced by classically activated neuroinflammatory microglia. The researchers showed that these A1 astrocytes lose beneficial functions and instead induce the death of neurons and oligodendrocytes. Additionally, the study found that blocking the formation of A1 astrocytes prevents the death of axotomized central nervous system neurons, and that A1 astrocytes are abundant in various human neurodegenerative diseases.
Key findings
- A subtype of reactive astrocytes, which we termed A1, is induced by classically activated neuroinflammatory microglia.
- Activated microglia induce A1 astrocytes by secreting Il-1α, TNF and C1q, and that these cytokines together are necessary and sufficient to induce A1 astrocytes.
- A1 astrocytes lose the ability to promote neuronal survival, outgrowth, synaptogenesis and phagocytosis, and induce the death of neurons and oligodendrocytes.
- Death of axotomized CNS neurons in vivo is prevented when the formation of A1 astrocytes is blocked.
Why it matters
Reports that activated microglia induce reactive astrocytes that are toxic to nerve cells. It describes how one kind of brain cell acts on another and does not test any treatment in people.
Study details
- Evidence strengthLow
How this study scored 68/100
Published in a top-tier 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 | 10 / 10 | Tier 1 — top-tier general journal (Nature) |
| Journal's citation record | 4 / 4 | Nature: journal h-index 1,841 (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 | 2 / 5 | 2017 — within 10 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 | 7 / 7 | Cited 7,921 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 720.1 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 6 / 6 | Cited 217.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 5 / 6 | Cited by 119 other studies in this library |
| Still being cited | 4 / 4 | Cited 2,881 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Ben A. Barres: h-index 122 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 12 institution(s) in 5 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28099414) |
| Free to read | 2 / 2 | Free to read |
| Total | 68 / 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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., et al. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature. https://doi.org/10.1038/nature21029
Vancouver
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017. doi:10.1038/nature21029. PMID: 28099414.
BibTeX
@article{liddelow2017-28099414,
author = {Liddelow, Shane A. and Guttenplan, Kevin A. and Clarke, Laura E. and Bennett, F. Chris and Bohlen, Christopher J. and Schirmer, Lucas and Bennett, Mariko L. and Münch, Alexandra E. and others},
title = {{Neurotoxic reactive astrocytes are induced by activated microglia}},
journal = {Nature},
year = {2017},
doi = {10.1038/nature21029},
pmid = {28099414},
url = {https://doi.org/10.1038/nature21029}
}
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