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Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia
Fine SM, Angel RA, Perry SW, Epstein LG, Rothstein JD, Dewhurst S, Gelbard HA.. The Journal of biological chemistry, 1996-06-01
Topic: Brain proteins, microglia and lab models
Human immunodeficiency virus (HIV) infection is commonly associated with neurological disease that occurs in the apparent absence of extensive infection of brain cells by HIV, suggesting that indirect mechanisms account for neuropathogenesis in the CNS, perhaps including changes in the normal neuroprotective functions of astrocytes. To test this hypothesis, we examined the effect of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFalpha), produced by HIV-1-infected macrophages and microglia, on glutamate transport by primary human fetal astrocytes (PHFAs). A dose-dependent inhibition of high affinity glutamate uptake sites was observed 12-24 h after addition of exogenous recombinant human TNFalpha to PHFAs.
Key findings
- To test this hypothesis, we examined the effect of the pro-inflammatory cytokine, tumor necrosis factor alpha (TNFalpha), produced by HIV-1-infected macrophages and microglia, on glutamate transport by primary human fetal astrocytes (PHFAs).
- A dose-dependent inhibition of high affinity glutamate uptake sites was observed 12-24 h after addition of exogenous recombinant human TNFalpha to PHFAs.
- This effect was specific since it was blocked by a neutralizing monoclonal antibody directed against TNFalpha.
- Furthermore, the inhibitory effect was reproduced by a monoclonal antibody that is an agonist at the 55-kDa TNF receptor.
Why it matters
In human fetal astrocytes grown in the laboratory, the inflammatory cytokine TNFalpha reduced glutamate uptake in a dose-dependent way. This is a cell study related to HIV-1 dementia, not a treatment or prevention for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 47/100
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 (The Journal of biological chemistry) |
| Journal's citation record | 4 / 4 | Journal of Biological Chemistry: journal h-index 780 (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 | 1 / 5 | 1996 — older than 20 years, still counted |
| 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 | 6 / 7 | Cited 325 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.2 citations a year over 32 year(s) since 1996 |
| Impact for its field and year | 4 / 6 | Cited 11.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Harris A. Gelbard: h-index 54 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 8663435) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1074/jbc.271.26.15303
- PubMed: 8663435
- Original source →
- Free full text: Journal of Biological Chemistry →
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 7 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
Fine, S. M., Angel, R. A., Perry, S. W., Epstein, L. G., Rothstein, J. D., Dewhurst, S., et al. (1996). Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia. The Journal of biological chemistry. https://doi.org/10.1074/jbc.271.26.15303
Vancouver
Fine SM, Angel RA, Perry SW, Epstein LG, Rothstein JD, Dewhurst S, et al. Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia. The Journal of biological chemistry. 1996. doi:10.1074/jbc.271.26.15303. PMID: 8663435.
BibTeX
@article{fine1996-8663435,
author = {Fine, S. M. and Angel, R. A. and Perry, S. W. and Epstein, L. G. and Rothstein, J. D. and Dewhurst, S. and Gelbard, H. A.},
title = {{Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia}},
journal = {The Journal of biological chemistry},
year = {1996},
doi = {10.1074/jbc.271.26.15303},
pmid = {8663435},
url = {https://doi.org/10.1074/jbc.271.26.15303}
}
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