Cognitive Alterations in Old Mice Are Associated with Intestinal Barrier Dysfunction and Induced Toll-like Receptor 2 and 4 Signaling in Different Brain Regions

Autor(en)

Annette Brandt, Franziska Kromm, Angélica Hernández-Arriaga, Inés Martínez Sánchez, Haktan Övül Bozkir, Raphaela Staltner, Anja Baumann, Amélia Camarinha-Silva, Rochellys Diaz Heijtz, Ina Bergheim

Abstrakt

Emerging evidence implicate the ‘microbiota–gut–brain axis’ in cognitive aging and neuroinflammation; however, underlying mechanisms still remain to be elucidated. Here, we assessed if potential alterations in intestinal barrier function and microbiota composition as well as levels of two key pattern-recognition receptors namely Toll-like receptor (TLR) 2 and TLR4, in blood and different brain regions, and depending signaling cascades are paralleling aging associated alterations of cognition in healthy aging mice. Cognitive function was assessed in the Y-maze and intestinal and brain tissue and blood were collected in young (4 months old) and old (24 months old) male C57BL/6 mice to determine intestinal microbiota composition by Illumina amplicon sequencing, the concentration of TLR2 and TLR4 ligands in plasma and brain tissue as well as to determine markers of intestinal barrier function, senescence and TLR2 and TLR4 signaling. Cognitive function was significantly impaired in old mice. Also, in old mice, intestinal microbiota composition was significantly altered, while the relative abundance of Gram-negative or Gram-positive bacteria in the small and large intestines at different ages was not altered. Moreover, intestinal barrier function was impaired in small intestine of old mice, and the levels of TLR2 and TLR4 ligands were also significantly higher in both portal and peripheral blood. Furthermore, levels of TLR2 and TLR4 ligands, and downstream markers of TLR signaling were higher in the hippocampal and prefrontal cortex of old mice compared to young animals. Taken together, our results suggest that even in ‘healthy’ aging, cognitive function is impaired in mice going along with an increased intestinal translocation of TLR ligands and alterations of TLR signaling in several brain regions.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Universität Hohenheim, Karolinska Institute

Journal

Cells

Band

12

ISSN

2073-4409

DOI

https://doi.org/10.3390/cells12172153

Publikationsdatum

08-2023

Peer-reviewed

Ja

ÖFOS 2012

303009 Ernährungswissenschaften

Schlagwörter

ASJC Scopus Sachgebiete

Biochemistry, Genetics and Molecular Biology(all)

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/cognitive-alterations-in-old-mice-are-associated-with-intestinal-barrier-dysfunction-and-induced-tolllike-receptor-2-and-4-signaling-in-different-brain-regions(d908b6d1-2784-4464-843b-262c8a1b9f57).html