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Aging‐like changes in the transcriptome of irradiated microglia
Matthew D. Li, Terry C. Burns, Sunny Kumar, Alexander A. Morgan, Steven A. Sloan, Theo D. Palmer. Glia, 2015-02-17
Topic: Inflammation, microglia and astrocytes
Whole brain irradiation remains important in the management of brain tumors. Although necessary for improving survival outcomes, cranial irradiation also results in cognitive decline in long‐term survivors. A chronic inflammatory state characterized by microglial activation has been implicated in radiation‐induced brain injury. We here provide the first comprehensive transcriptional profile of irradiated microglia. Fluorescence‐activated cell sorting was used to isolate CD11b+ microglia from the hippocampi of C57BL/6 and Balb/c mice 1 month after 10 Gy cranial irradiation. Affymetrix gene expression profiles were evaluated using linear modeling and rank product analyses. One month after irradiation, a conserved irradiation signature across strains was identified, comprising 448 and 85 differentially up‐ and downregulated genes, respectively. Gene set enrichment analysis demonstrated enrichment for inflammation, including M1 macrophage‐associated genes, but also an unexpected enrichment for extracellular matrix and blood coagulation‐related gene sets, in contrast previously described microglial states. Weighted gene coexpression network analysis confirmed these findings and further revealed alterations in mitochondrial function. The RNA‐seq transcriptome of microglia 24‐h postradiation proved similar to the 1‐month transcriptome, but additionally featured alterations in apoptotic and lysosomal gene expression. Reanalysis of published aging mouse microglia transcriptome data demonstrated striking similarity to the 1‐month irradiated microglia transcriptome, suggesting that shared mechanisms may underlie aging and chronic irradiation‐induced cognitive decline. GLIA 2015;63:754–767
Key findings
- Although necessary for improving survival outcomes, cranial irradiation also results in cognitive decline in long‐term survivors.
- Gene set enrichment analysis demonstrated enrichment for inflammation, including M1 macrophage‐associated genes, but also an unexpected enrichment for extracellular matrix and blood coagulation‐related gene sets, in contrast previously described microglial states.
- Weighted gene coexpression network analysis confirmed these findings and further revealed alterations in mitochondrial function.
- Reanalysis of published aging mouse microglia transcriptome data demonstrated striking similarity to the 1‐month irradiated microglia transcriptome, suggesting that shared mechanisms may underlie aging and chronic irradiation‐induced cognitive decline.
Study details
- Evidence strengthLow
How this study scored 36/100
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. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 20 of the 56 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Glia) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 1 / 5 | 2015 — within 20 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 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 20 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 20 of the 56 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Li, M. D., Burns, T. C., Kumar, S., Morgan, A. A., Sloan, S. A., & Palmer, T. D. (2015). Aging‐like changes in the transcriptome of irradiated microglia. Glia. https://doi.org/10.1002/glia.22782
Vancouver
Li MD, Burns TC, Kumar S, Morgan AA, Sloan SA, Palmer TD. Aging‐like changes in the transcriptome of irradiated microglia. Glia. 2015. doi:10.1002/glia.22782.
BibTeX
@article{li2015-7e58f8dc,
author = {Li, Matthew D. and Burns, Terry C. and Kumar, Sunny and Morgan, Alexander A. and Sloan, Steven A. and Palmer, Theo D.},
title = {{Aging‐like changes in the transcriptome of irradiated microglia}},
journal = {Glia},
year = {2015},
doi = {10.1002/glia.22782},
url = {https://doi.org/10.1002/glia.22782}
}