{"id":4557,"date":"2020-06-22T17:22:18","date_gmt":"2020-06-22T21:22:18","guid":{"rendered":"https:\/\/ccna-ccnv.ca\/ccna_publication\/np03-a-microdose-lithium-formulation-blunts-early-amyloid-post-plaque-neuropathology-in-mcgill-r-thy1-app-alzheimer-like-transgenic-rats-2\/"},"modified":"2024-12-03T14:57:00","modified_gmt":"2024-12-03T19:57:00","slug":"np03-a-microdose-lithium-formulation-blunts-early-amyloid-post-plaque-neuropathology-in-mcgill-r-thy1-app-alzheimer-like-transgenic-rats-2","status":"publish","type":"ccna_publication","link":"https:\/\/ccna-ccnv.ca\/fr\/ccna_publication\/np03-a-microdose-lithium-formulation-blunts-early-amyloid-post-plaque-neuropathology-in-mcgill-r-thy1-app-alzheimer-like-transgenic-rats-2\/","title":{"rendered":"NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats."},"content":{"rendered":"<h2 class=\"title\">Abstract<\/h2>\n<div id=\"en-abstract\" class=\"abstract-content selected\">\n<p>Epidemiological, preclinical, and clinical studies have suggested a role for microdose lithium in reducing Alzheimer&rsquo;s disease (AD) risk by modulating key mechanisms associated with AD pathology. The novel microdose lithium formulation, NP03, has disease-modifying effects in the McGill-R-Thy1-APP transgenic rat model of AD-like amyloidosis at pre-plaque stages, before frank amyloid-\u03b2 (A\u03b2) plaque deposition, during which A\u03b2 is primarily intraneuronal. Here, we are interested in determining whether the positive effects of microdose lithium extend into early A\u03b2 post-plaque stages. We administered NP03 (40\u03bcg Li\/kg; 1 ml\/kg body weight) to McGill-R-Thy1-APP transgenic rats for 12 weeks spanning the transition phase from plaque-free to plaque-bearing. The effect of NP03 on remote working memory was assessed using the novel object recognition task. Levels of human A\u03b238, A\u03b240, and A\u03b242 as well as levels of pro-inflammatory mediators were measured in brain-extracts and plasma using electrochemiluminescent assays. Mature A\u03b2 plaques were visualized with a thioflavin-S staining. Vesicular acetylcholine transporter (VAChT) bouton density and levels of chemokine (C-X-C motif) ligand 1 (CXCL1), interleukin-6 (IL-6), and 4-hydroxynonenal (4-HNE) were probed using quantitative immunohistochemistry. During the early A\u03b2 post-plaque stage, we find that NP03 rescues functional deficits in object recognition, reduces loss of cholinergic boutons in the hippocampus, reduces levels of soluble and insoluble cortical A\u03b242 and reduces hippocampal A\u03b2 plaque number. In addition, NP03 reduces markers of neuroinflammation and cellular oxidative stress. Together these results indicate that microdose lithium NP03 is effective at later stages of amyloid pathology, after appearance of A\u03b2 plaques.<\/p>\n<\/div>\n","protected":false},"author":19,"featured_media":0,"template":"","meta":{"_acf_changed":false},"studies-relation":[],"class_list":["post-4557","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>NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats. - 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\/np03-a-microdose-lithium-formulation-blunts-early-amyloid-post-plaque-neuropathology-in-mcgill-r-thy1-app-alzheimer-like-transgenic-rats-2\/\" \/>\n<meta property=\"og:locale\" content=\"fr_CA\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"NP03, a Microdose Lithium Formulation, Blunts Early Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like Transgenic Rats. - 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