{"id":4629,"date":"2020-09-01T12:22:18","date_gmt":"2020-09-01T16:22:18","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/differential-effects-of-chronic-immunosuppression-on-behavioral-epigenetic-and-alzheimers-diseaseassociated-markers-in-3xtg-ad-mice-2\/"},"modified":"2024-12-03T14:57:13","modified_gmt":"2024-12-03T19:57:13","slug":"differential-effects-of-chronic-immunosuppression-on-behavioral-epigenetic-and-alzheimers-diseaseassociated-markers-in-3xtg-ad-mice-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/differential-effects-of-chronic-immunosuppression-on-behavioral-epigenetic-and-alzheimers-diseaseassociated-markers-in-3xtg-ad-mice-2\/","title":{"rendered":"Differential Effects of Chronic Immunosuppression on Behavioral, Epigenetic and Alzheimer\u2019s DiseaseAssociated Markers in 3xTg-AD Mice"},"content":{"rendered":"<div class=\"align-m\">\n<h2>Abstract<\/h2>\n<\/div>\n<div class=\"collapsable-text readability is-active\">\n<p>Circulating autoantibodies and sex-dependent discrepancy in prevalence are unexplained phenomena of Alzheimer\u2019s disease (AD). Using the 3xTg-AD mouse model, we reported that adult males show early manifestations of systemic autoimmunity, increased emotional reactivity, enhanced expression of the histone variant macroH2A1 in the cerebral cortex, and loss of plaque\/tangle pathology. Conversely, adult females display less severe autoimmunity and retain their AD-like phenotype. This study examines the link between immunity and other traits of the current 3xTg-AD model. Young 3xTg-AD and wild-type mice drank a sucrose-laced 0.4\u00a0mg\/ml solution of the immunosuppressant cyclophosphamide on weekends for 5 months. After behavioral phenotyping at 2 and 6 months of age, we assessed organ mass, serologic markers of autoimmunity, molecular markers of early AD pathology and expression of genes associated with neurodegeneration. Chronic immunosuppression prevented hematocrit drop and reduced soluble A\u03b2 in 3xTg-AD males while normalizing the expression of histone variant macroH2A1 in 3xTg-AD females. This treatment also reduced hepatosplenomegaly, lowered autoantibody levels, and increased the effector T cell population while decreasing the proportion of regulatory T cells in both sexes. Exposure to cyclophosphamide, however, neither prevented reduced brain mass and BDNF expression nor normalized increased tau and anxiety-related behaviors. The results suggest that systemic autoimmunity increases soluble A\u03b2 production and affects transcriptional regulation of macroH2A1 in a sex-related manner. Despite the complexity of multisystem interactions, 3xTg-AD mice can be a useful\u00a0<em>in vivo<\/em>\u00a0model for exploring the regulatory role of autoimmunity in the etiology of AD-like neurodegenerative disorders.<\/p>\n<p>(Team 2)<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4629","ccna_publication","type-ccna_publication","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Differential Effects of Chronic Immunosuppression on Behavioral, Epigenetic and Alzheimer\u2019s DiseaseAssociated Markers in 3xTg-AD Mice - CCNA - CCNV<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/differential-effects-of-chronic-immunosuppression-on-behavioral-epigenetic-and-alzheimers-diseaseassociated-markers-in-3xtg-ad-mice-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Differential Effects of Chronic Immunosuppression on Behavioral, Epigenetic and Alzheimer\u2019s DiseaseAssociated Markers in 3xTg-AD Mice - 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