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High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex
Zhang X, Dong F, Ren J, Driscoll MJ, Culver B.. Experimental neurology, 2005-02-01
Topic: Brain proteins, microglia and lab models
Epidemiological and experimental studies have suggested that high dietary intake of fats is associated with cognitive decline and a significantly increased risk of dementia. Since oxidative stress and inflammation have been speculated to be critical mechanisms underlying neurodegenerative diseases, we hypothesized that a high fat (HF) diet might induce cerebral oxidative stress or neural inflammation and subsequently contribute to the high risk of dementia. To test this hypothesis, male rats were placed on either a HF diet or a low fat (LF) diet starting at 1 month of age and lasting for 5 months. Intracellular reactive oxidative species (ROS) generation in the cerebral cortex was measured by the oxidant-sensitive dye 5-(6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA). Cortical tissue concentration of prostaglandin E(2) (PGE(2)) was determined using an enzymatic immunoassay. Expression of NADPH oxidase subunits, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), nuclear transcription factor NF(kappa)-B (NF-kappaB) p65 subunit, Ikappa B(IkappaB), and phospho-Ikappa B(phospho-IkappaB) was evaluated by Western blot analysis. The HF diet significantly increased ROS generation and expression of gp91(phox), p22(phox), p47(phox), and p67(phox) NADPH oxidase subunits in cerebral cortex. Elevated PGE(2) levels and markedly increased COX-2 expression suggested a neural inflammatory response in response to excessive fat intake. These findings were further supported by significantly increased phospho-IkappaB and nuclear NF-kappaB expression that suggested a role of IkappaB phosphorylation in HF diet-induced NF-kappaB translocation. The present study revealed that HF diet induced neural oxidative stress, inflammation, and NF-kappaB activation in rat cerebral cortex, and provided novel evidence regarding the link between high dietary fat and increased risk of dementia.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zhang, X., Dong, F., Ren, J., Driscoll, M. J., & Culver, B. (2005). High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex. Experimental neurology. https://doi.org/10.1016/j.expneurol.2004.10.011
Vancouver
Zhang X, Dong F, Ren J, Driscoll MJ, Culver B. High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex. Experimental neurology. 2005. doi:10.1016/j.expneurol.2004.10.011. PMID: 15649487.
BibTeX
@article{zhang2005-15649487,
author = {Zhang, X. and Dong, F. and Ren, J. and Driscoll, M. J. and Culver, B.},
title = {{High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex}},
journal = {Experimental neurology},
year = {2005},
doi = {10.1016/j.expneurol.2004.10.011},
pmid = {15649487},
url = {https://doi.org/10.1016/j.expneurol.2004.10.011}
}
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Key findings
- Epidemiological and experimental studies have suggested that high dietary intake of fats is associated with cognitive decline and a significantly increased risk of dementia.
- The HF diet significantly increased ROS generation and expression of gp91(phox), p22(phox), p47(phox), and p67(phox) NADPH oxidase subunits in cerebral cortex.
- These findings were further supported by significantly increased phospho-IkappaB and nuclear NF-kappaB expression that suggested a role of IkappaB phosphorylation in HF diet-induced NF-kappaB translocation.
- The present study revealed that HF diet induced neural oxidative stress, inflammation, and NF-kappaB activation in rat cerebral cortex, and provided novel evidence regarding the link between high dietary fat and increased risk of dementia.
Why it matters
In rats, a high fat diet increased oxidative stress and inflammation in the cerebral cortex, which the authors suggest may contribute to dementia risk. This is animal research and does not show that dietary fat reduction prevents dementia in humans.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Experimental neurology) |
| Journal's citation record | 3 / 4 | Experimental Neurology: journal h-index 271 (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 | 2005 — 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 | Laboratory or animal study (title names “rat”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 280 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.2 citations a year over 23 year(s) since 2005 |
| Impact for its field and year | 3 / 6 | Cited 3.2× 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 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author B. Culver: h-index 8 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Wyoming: institution h-index 481 (OpenAlex) |
| Multicenter collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 15649487) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 38 / 100 | — |
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