{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:35:53Z","timestamp":1790562953026,"version":"4.1.0"},"reference-count":96,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T00:00:00Z","timestamp":1693094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement","award":["859890"],"award-info":[{"award-number":["859890"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement","award":["P35271"],"award-info":[{"award-number":["P35271"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement","award":["I04844"],"award-info":[{"award-number":["I04844"]}]},{"name":"the Herzfelder Family Foundation\/Austrian Science Fund FWF","award":["859890"],"award-info":[{"award-number":["859890"]}]},{"name":"the Herzfelder Family Foundation\/Austrian Science Fund FWF","award":["P35271"],"award-info":[{"award-number":["P35271"]}]},{"name":"the Herzfelder Family Foundation\/Austrian Science Fund FWF","award":["I04844"],"award-info":[{"award-number":["I04844"]}]},{"name":"the Austrian Science Fund FWF","award":["859890"],"award-info":[{"award-number":["859890"]}]},{"name":"the Austrian Science Fund FWF","award":["P35271"],"award-info":[{"award-number":["P35271"]}]},{"name":"the Austrian Science Fund FWF","award":["I04844"],"award-info":[{"award-number":["I04844"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Emerging evidence implicate the \u2018microbiota\u2013gut\u2013brain axis\u2019 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 \u2018healthy\u2019 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.<\/jats:p>","DOI":"10.3390\/cells12172153","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T02:23:25Z","timestamp":1693189405000},"page":"2153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Cognitive Alterations in Old Mice Are Associated with Intestinal Barrier Dysfunction and Induced Toll-like Receptor 2 and 4 Signaling in Different Brain Regions"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3934-747X","authenticated-orcid":false,"given":"Annette","family":"Brandt","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Kromm","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica","family":"Hern\u00e1ndez-Arriaga","sequence":"additional","affiliation":[{"name":"Animal Nutrition Department, Institute of Animal Science, University of Hohenheim, 70593 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e9s","family":"Mart\u00ednez S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institute, Biomedicum, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8174-0515","authenticated-orcid":false,"given":"Haktan \u00d6v\u00fcl","family":"Bozkir","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphaela","family":"Staltner","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Baumann","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7814-6569","authenticated-orcid":false,"given":"Am\u00e9lia","family":"Camarinha-Silva","sequence":"additional","affiliation":[{"name":"Animal Nutrition Department, Institute of Animal Science, University of Hohenheim, 70593 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rochellys Diaz","family":"Heijtz","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Karolinska Institute, Biomedicum, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina","family":"Bergheim","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/S0140-6736(20)30977-6","article-title":"Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950\u20132019: A comprehensive demographic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Collaborators","year":"2020","journal-title":"Lancet"},{"key":"ref_2","unstructured":"Eurostat (2022, December 16). 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