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Defining the Intestinal eCBome and Oxylipin Signaling Systems in a TDP‐43 Mouse Model of Frontotemporal Dementia
Hayatte-Dounia Mir, Giada Giorgini, Irene Santos‐García, Elizabeth Dumais, Carmen Rodríguez‐Cueto, Eva de Lago, Cristoforo Silvestri, Nicolas Flamand et al.. The FASEB Journal, 2026-01-12
Topic: Brain proteins, microglia and lab models
Frontotemporal dementia (FTD) is a group of early onset and progressive disorders, characterized by degeneration in the frontal and temporal lobes, and subsequent deterioration in cognition, personality, social behavior, and language, with aggregates of the RNA-binding protein TDP-43 being present in ~45% of the cases. We reported alterations of the endocannabinoidome (eCBome) in the brain of a TDP-43 mouse model of FTD. Here we investigated the small intestinal eCBome, oxylipins, and, preliminarily, the gut microbiome. The duodenum, jejunum, and ileum of TDP-43 overexpressing versus wildtype mice were investigated. Lipid mediators were measured by HPLC-MS/MS, and mRNA expression of genes involved in eCBome mediator action and metabolism, or intestinal permeability and inflammation, was analyzed by qPCR. Intestinal content microbiota composition and fecal short-chain fatty acids were studied by 16S DNA sequencing and GC-FID, respectively. Alterations were observed in TDP-43 mice for polyunsaturated fatty acids, N-acyl-ethanolamines, and oxylipins in the duodenum and the jejunum, and for oxylipins and 2-monoacylglycerols in the ileum. Regarding the receptors, mRNA expression of Cnr1 and Gpr119 was increased in the ileum, and that of Pparg in the duodenum, where Gpr55 was instead down-regulated. Regarding the enzymes, Faah and Napepld expression was increased in the ileum. Preliminary gut microbiota data suggest increases of Paraprevotella and Monoglobus in the feces, of DNF00809 in the ileum, and of Butyricicoccus, Candidatus_Arthromitus, and Oscillospira in the cecum, where Paraprevotella, Mucispirillum, and Akkermansia were instead decreased. Fecal acetic, butyric, and isobutyric acid were reduced. We suggest the existence of lipid signal-mediated gut-brain interactions in FTD.
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APA 7th
Mir, H.-D., Giorgini, G., Santos‐García, I., Dumais, E., Rodríguez‐Cueto, C., de Lago, E., et al. (2026). Defining the Intestinal eCBome and Oxylipin Signaling Systems in a TDP‐43 Mouse Model of Frontotemporal Dementia. The FASEB Journal. https://doi.org/10.1096/fj.202502312rr
Vancouver
Mir H.-D, Giorgini G, Santos‐García I, Dumais E, Rodríguez‐Cueto C, de Lago E, et al. Defining the Intestinal eCBome and Oxylipin Signaling Systems in a TDP‐43 Mouse Model of Frontotemporal Dementia. The FASEB Journal. 2026. doi:10.1096/fj.202502312rr. PMID: 41524247.
BibTeX
@article{mir2026-41524247,
author = {Mir, Hayatte-Dounia and Giorgini, Giada and Santos‐García, Irene and Dumais, Elizabeth and Rodríguez‐Cueto, Carmen and de Lago, Eva and Silvestri, Cristoforo and Flamand, Nicolas and others},
title = {{Defining the Intestinal eCBome and Oxylipin Signaling Systems in a TDP‐43 Mouse Model of Frontotemporal Dementia}},
journal = {The FASEB Journal},
year = {2026},
doi = {10.1096/fj.202502312rr},
pmid = {41524247},
url = {https://doi.org/10.1096/fj.202502312rr}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- The duodenum, jejunum, and ileum of TDP-43 overexpressing versus wildtype mice were investigated.
Why it matters
In a TDP-43 overexpressing mouse model of frontotemporal dementia, this study found alterations in the small intestinal endocannabinoidome, oxylipins and, preliminarily, the gut microbiome compared with wildtype mice. These are animal findings about intestinal signaling and no treatment, cure or prevention for Alzheimer's disease is tested.
Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The FASEB Journal) |
| Journal's citation record | 3 / 4 | The FASEB Journal: journal h-index 401 (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 | 5 / 5 | 2026 — within 1 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 “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 4.0× 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 | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Vincenzo Di Marzo: h-index 160 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | National Research Council: institution h-index 840 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41524247) |
| Free to read | 2 / 2 | Free to read |
| Total | 41 / 100 | — |
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