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Defining the Intestinal eCBome and Oxylipin Signaling Systems in a TDP-43 Mouse Model of Frontotemporal Dementia
Hayatte-Dounia Mir1,2, Giada Giorgini1,2,3,4, Irene Santos-García5,6,7
1Département de Médicine (DMED), Centre de Recherche de l'Institut Universitaire de Pneumologie et Cardiologie (CRIUCPQ), Faculté de Médicine (FMED), Université Laval, Québec, Canada.
Summary
This study reveals altered lipid signaling and gut bacteria in a mouse model of frontotemporal dementia (FTD). These changes suggest potential gut-brain interactions mediated by lipid signals in FTD.
Area of Science:
- Neuroscience
- Gastroenterology
- Biochemistry
Background:
- Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder.
- TDP-43 protein aggregates are found in approximately 45% of FTD cases.
- Previous research indicated endocannabinoidome (eCBome) alterations in the brain of an FTD mouse model.
Purpose of the Study:
- To investigate the small intestinal endocannabinoidome (eCBome), oxylipins, and gut microbiome in a TDP-43 mouse model of FTD.
- To explore potential gut-brain interactions in FTD pathogenesis.
Main Methods:
- Analysis of lipid mediators (eCBome, oxylipins) in the duodenum, jejunum, and ileum using HPLC-MS/MS.
- Quantification of mRNA expression for genes related to eCBome, intestinal permeability, and inflammation via qPCR.
- Assessment of gut microbiota composition (16S DNA sequencing) and fecal short-chain fatty acids (GC-FID).
Main Results:
- Significant alterations in polyunsaturated fatty acids, N-acyl-ethanolamines, and oxylipins were observed in the duodenum and jejunum of TDP-43 mice.
- Changes in oxylipins and 2-monoacylglycerols were noted in the ileum.
- Upregulation of Cnr1, Gpr119, and Pparg, and downregulation of Gpr55 were detected in specific intestinal segments.
- Alterations in gut microbiota composition and reduced fecal short-chain fatty acids were observed.
Conclusions:
- The study identified significant alterations in the small intestinal lipid mediators and gut microbiome in a TDP-43 mouse model of FTD.
- These findings support the hypothesis of lipid signal-mediated gut-brain interactions contributing to FTD.
- Further research into these gut-brain axis disruptions may offer novel therapeutic targets for FTD.
