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Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice
Zou Y, Wang C, Li H, Zhong M, Lin J, Hu Y, Chen Z, Gan CL.. Frontiers in pharmacology, 2024-10-31
Topic: Brain proteins, microglia and lab models
Clinical studies have shown that epileptic seizures worsen Alzheimer's disease (AD) pathology and related cognitive deficits; however, the underlying mechanism is unclear. To assess the effects of seizures on the progression of AD, chronic temporal lobe epilepsy was induced in five familial AD mutation (5×FAD) mice by kindling with the chemoconvulsant pentylenetetrazole (PTZ) at 3-3.5 months of age. The amyloidogenic pathway, tauopathy, synaptic damage, neuronal death, neurological inflammatory response and associated kinase signaling pathway dysregulation were examined at 9 months of age. We found that APP, p-APP, BACE1, Aβ and kinase-associated p-tau levels were elevated after PTZ kindling in 5×FAD mice. In addition, PTZ kindling exacerbated hippocampal synaptic damage and neuronal cell death, as determined by scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, respectively. Finally, the levels of the neuroinflammation markers GFAP and Iba1, as well as the inflammatory cytokine IL-1β, were increased after PTZ insult. PTZ kindling profoundly exacerbated extracellular regulated kinase (ERK)-death-associated protein kinase (DAPK) signaling pathway overactivation, and acute ERK inhibitor treatment downregulated Aβ production and p-APP and p-tau levels in epileptic 5×FAD mice. In addition, long-term use of the antiseizure drug carbamazepine (CBZ) alleviated seizure-induced accelerated amyloid and tau pathology and ERK-DAPK overactivation in 5×FAD mice. Collectively, these results demonstrate that seizure-induced increases in AD-like neuropathology in 5×FAD mice are partially regulated by the ERK-DAPK pathway, suggesting that the ERK-DAPK axis could be a new therapeutic target for the treatment of AD patients with comorbid seizures.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Zou, Y., Wang, C., Li, H., Zhong, M., Lin, J., Hu, Y., et al. (2024). Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice. Frontiers in pharmacology. https://doi.org/10.3389/fphar.2024.1500105
Vancouver
Zou Y, Wang C, Li H, Zhong M, Lin J, Hu Y, et al. Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice. Frontiers in pharmacology. 2024. doi:10.3389/fphar.2024.1500105. PMID: 39545066.
BibTeX
@article{zou2024-39545066,
author = {Zou, Y. and Wang, C. and Li, H. and Zhong, M. and Lin, J. and Hu, Y. and Chen, Z. and Gan, C. L.},
title = {{Epileptic seizures induced by pentylenetetrazole kindling accelerate Alzheimer-like neuropathology in 5×FAD mice}},
journal = {Frontiers in pharmacology},
year = {2024},
doi = {10.3389/fphar.2024.1500105},
pmid = {39545066},
url = {https://doi.org/10.3389/fphar.2024.1500105}
}
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 8 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.
Key findings
- Clinical studies have shown that epileptic seizures worsen Alzheimer's disease (AD) pathology and related cognitive deficits; however, the underlying mechanism is unclear.
- We found that APP, p-APP, BACE1, Aβ and kinase-associated p-tau levels were elevated after PTZ kindling in 5×FAD mice.
- Collectively, these results demonstrate that seizure-induced increases in AD-like neuropathology in 5×FAD mice are partially regulated by the ERK-DAPK pathway, suggesting that the ERK-DAPK axis could be a new therapeutic target for the treatment of AD patients with comorbid seizures.
Why it matters
In 5×FAD mice, induced seizures increased Alzheimer-like brain pathology, and an ERK inhibitor reduced some of these changes. This is an animal study, so it does not establish any treatment or prevention for people with Alzheimer's disease.
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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 (Frontiers in pharmacology) |
| Journal's citation record | 2 / 4 | Frontiers in Pharmacology: journal h-index 242 (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 | 4 / 5 | 2024 — within 3 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 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 13 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.2 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 3 / 6 | Cited 3.1× 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 | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Chen‐Ling Gan: h-index 13 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Fujian Medical University: institution h-index 277 (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 39545066) |
| Free to read | 2 / 2 | Free to read |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fphar.2024.1500105
- PubMed: 39545066
- Original source →
- Free full text: Frontiers in Pharmacology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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