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Neurobiology of ammonia
Felipo V, Butterworth RF.. Progress in neurobiology, 2002-07-01
Topic: Brain proteins, microglia and lab models
Hyperammonemia resulting from inherited urea cycle enzyme deficiencies or liver failure results in severe central nervous system dysfunction including brain edema, convulsions and coma. Neuropathologic evaluation in these disorders reveals characteristic alterations of astrocyte morphology ranging from cell swelling (acute hyperammonemia) to Alzheimer Type II astrocytosis (chronic hyperammonemia). Having no effective urea cycle, brain relies on glutamine synthesis for the removal of excess ammonia and the enzyme responsible, glutamine synthetase, has a predominantly astrocytic localization.
Key findings
- Neuropathologic evaluation in these disorders reveals characteristic alterations of astrocyte morphology ranging from cell swelling (acute hyperammonemia) to Alzheimer Type II astrocytosis (chronic hyperammonemia).
- Having no effective urea cycle, brain relies on glutamine synthesis for the removal of excess ammonia and the enzyme responsible, glutamine synthetase, has a predominantly astrocytic localization.
- Accumulation of ammonia in brain results in a redistribution of cerebral blood flow and metabolism from cortical to sub-cortical structures.
- In addition to changes in astrocyte morphology, increased brain ammonia concentrations result in alterations in expression of key astrocyte proteins including glial fibrillary acidic protein, glutamate and glycine transporters and "peripheral-type" (mitochondrial) benzodiazepine receptors.
Why it matters
This review concerns hyperammonemia from urea cycle enzyme deficiencies or liver failure, which causes astrocyte changes including Alzheimer Type II astrocytosis. It is about ammonia neurobiology, not Alzheimer's disease, and reports no treatment, cure or prevention for Alzheimer's.
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 (Progress in neurobiology) |
| Journal's citation record | 3 / 4 | Progress in Neurobiology: journal h-index 325 (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 | 2002 — 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 621 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 23.9 citations a year over 26 year(s) since 2002 |
| Impact for its field and year | 4 / 6 | Cited 10.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 47 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Roger F. Butterworth: h-index 81 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Université de Montréal: institution h-index 1,020 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 12207972) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
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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. Check the citation against the original before you use it.
APA 7th
Felipo, V., & Butterworth, R. F. (2002). Neurobiology of ammonia. Progress in neurobiology. https://doi.org/10.1016/s0301-0082(02)00019-9
Vancouver
Felipo V, Butterworth RF. Neurobiology of ammonia. Progress in neurobiology. 2002. doi:10.1016/s0301-0082(02)00019-9. PMID: 12207972.
BibTeX
@article{felipo2002-12207972,
author = {Felipo, V. and Butterworth, R. F.},
title = {{Neurobiology of ammonia}},
journal = {Progress in neurobiology},
year = {2002},
doi = {10.1016/s0301-0082(02)00019-9},
pmid = {12207972},
url = {https://doi.org/10.1016/s0301-0082(02)00019-9}
}
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