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Neurosci."],"abstract":"<jats:p>Bacterial infections are a common cause of morbidity and mortality in the elderly, and particularly in individuals with a neurodegenerative disease. Experimental models of neurodegeneration have shown that LPS-induced systemic inflammation increases neuronal damage, a process thought to be mediated by activation of \u201cprimed\u201d microglia. The effects of a real systemic bacterial infection on the innate immune cells in the brain and neuronal networks are less well described, and therefore, in this study we use the ME7 prion model to investigate the alterations in microglia activation and phenotype and synaptic markers in response to a low grade, live bacterial infection. Mice with or without a pre-existing ME7 prion-induced neurodegenerative disease were given a single systemic injection of live <jats:italic>Salmonella typhimurium<\/jats:italic> at early or mid-stage of disease progression. Immune activation markers CD11b and MHCII and pro-inflammatory cytokines were analyzed 4 weeks post-infection. Systemic infection with <jats:italic>S. typhimurium<\/jats:italic> resulted in an exaggerated inflammatory response when compared to ME7 prion mice treated with saline. These changes to inflammatory markers were most pronounced at mid-stage disease. Analysis of synaptic markers in ME7 prion mice revealed a significant reduction of genes that are associated with early response in synaptic plasticity, extracellular matrix structure and post-synaptic density, but no further reduction following systemic infection. In contrast, analysis of activity-related neuronal receptors involved in development of learning and memory, such as <jats:italic>Grm1<\/jats:italic> and <jats:italic>Grin2a<\/jats:italic>, showed a significant decrease in response to systemic bacterial challenge. These changes were observed early in the disease progression and associated with reduced burrowing activity. The exaggerated innate immune activation and altered expression of genes linked to synaptic plasticity may contribute to the onset and\/or progression of neurodegeneration.<\/jats:p>","DOI":"10.3389\/fnins.2021.760721","type":"journal-article","created":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T08:35:28Z","timestamp":1641285328000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Systemic Inflammation Accelerates Changes in Microglial and Synaptic Markers in an Experimental Model of Chronic Neurodegeneration"],"prefix":"10.3389","volume":"15","author":[{"given":"Joe K.","family":"Chouhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"P\u00fcntener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven G.","family":"Booth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Teeling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.neuropharm.2013.07.004","article-title":"Therapeutics of Alzheimer\u2019s disease: past, present and future.","volume":"76","author":"Anand","year":"2014","journal-title":"Neuropharmacology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"105292","DOI":"10.1016\/j.nbd.2021.105292","article-title":"Bacterial sepsis increases hippocampal fibrillar amyloid plaque load and neuroinflammation in a mouse model of Alzheimer\u2019s disease.","volume":"152","author":"Basak","year":"2021","journal-title":"Neurobiol. 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