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APOE4 mouse models have provided advances in the understanding of disease pathogenesis, but unaccounted variables like rodent housing status may hinder translational outcomes. Non-sterile aspects like food and bedding can be major sources of changes in rodent microflora. Alterations in intestinal microbial ecology can cause mucosal barrier impairment and increase pro-inflammatory signals. The present study examined the role of sterile and non-sterile food and housing on redox indicators and the immune status of humanized-<jats:italic>APOE4<\/jats:italic> knock-in mice (hAPOe4). hAPOE4 mice were housed under sterile conditions until 22 months of age, followed by the transfer of a cohort of mice to non-sterile housing for 2\u00a0months. At 24\u00a0months of age, the redox\/immunologic status was evaluated by flow cytometry\/ELISA. hAPOE4 females housed under non-sterile conditions exhibited: (1) higher neuronal and microglial oxygen radical production and (2) lower CD68<jats:sup>+<\/jats:sup> microglia (brain) and CD8<jats:sup>+<\/jats:sup> T cells (periphery) compared to sterile-housed mice. In contrast, hAPOE4 males in non-sterile housing exhibited: (1) higher MHCII<jats:sup>+<\/jats:sup> microglia and CD11b<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells (brain) and (2) higher CD11b<jats:sup>+<\/jats:sup>CD4<jats:sup>+<\/jats:sup> T cells and levels of lipopolysaccharide-binding protein and inflammatory cytokines in the periphery relative to sterile-housed mice. This study demonstrated that sterile vs. non-sterile housing conditions are associated with the activation of redox and immune responses in the brain and periphery in a sex-dependent manner. Therefore, housing status may contribute to variable outcomes in both the brain and periphery.<\/jats:p>","DOI":"10.1007\/s00221-023-06763-x","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T16:02:22Z","timestamp":1704988942000},"page":"543-557","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice"],"prefix":"10.1007","volume":"242","author":[{"given":"E. M.","family":"Reyes-Reyes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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