Browsing by Subject "Plaques"

Now showing 1 - 4 of 4
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    Author Correction: FAM222A encodes a protein which accumulates in plaques in Alzheimer’s disease
    (Springer Nature, 2022-07-11) Yan, Tingxiang; Liang, Jingjing; Gao, Ju; Wang, Luwen; Fujioka, Hisashi; The Alzheimer Disease Neuroimaging Initiative; Zhu, Xiaofeng; Wang, Xinglong; Radiology and Imaging Sciences, School of Medicine
    Correction to: Nature Communications 10.1038/s41467-019-13962-0, published online 21 January 2020. In the original version of the manuscript, the image shown in Figure 4g, bottom row (Aβ1–42 + rAggregatin), under “6h” was incorrect. This image incorrectly showed the same sample as shown in the original Figure 4g, top row (Aβ1–42), under “0.5h”.
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    In vitro Cariostatic effects of cinnamon water extract on nicotine-induced Streptococcus mutans biofilm
    (BMC, 2020-02-11) Alshahrani, Abdulaziz M.; Gregory, Richard L.; Cariology, Operative Dentistry and Dental Public Health, School of Dentistry
    Background: Dental caries is one of the most prevalent chronic oral diseases worldwide. Dental caries is mainly associated with Streptococcus mutans and the Lactobacillus species. A specific relationship was found between nicotine and S. mutans growth as the presence of nicotine increased S. mutans biofilm formation. Nicotine is able to increase the number of S. mutans and extracellular polysaccharide (EPS) synthesis. Among the widely used herbs and spices is cinnamon which demonstrated a strong antibacterial activity against a wide variety of bacteria including S. mutans and showed the ability to inhibit S. mutans biofilm formation. Cinnamon essential oil, obtained from the leaves of C. zeylanicum, has been demonstrated to be effective against S. mutans and Lactobacillus acidophilus, which are partially responsible for dental plaque formation and caries development. The aim of this study was to identify the effects of nicotine exposure on the inhibitory effects of cinnamon water extract on S. mutans biofilm formation. Materials and methods: A 24-h culture of S. mutans UA159 in microtiter plates was treated with varying nicotine concentrations (0-32 mg/ml) in Tryptic Soy broth supplemented with 1% sucrose (TSBS) with or without a standardized concentration (2.5 mg/ml) of cinnamon water extract. A spectrophotometer was used to determine total growth absorbance and planktonic growth. The microtiter plate wells were washed, fixed and stained with crystal violet dye and the absorbance measured to determine biofilm formation. Results: The presence of 2.5 mg/ml cinnamon water extract inhibits nicotine-induced S. mutans biofilm formation from 34 to 98% at different concentrations of nicotine (0-32 mg/ml). Conclusion: The results demonstrated nicotine-induced S. mutans biofilm formation is decreased from 34 to 98% in the presence of 2.5 mg/ml cinnamon water extract. This provides further evidence about the biofilm inhibitory properties of cinnamon water extract and reconfirms the harmful effects of nicotine.
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    Microglia depletion rapidly and reversibly alters amyloid pathology by modification of plaque compaction and morphologies
    (Elsevier, 2020-08) Casali, Brad T.; MacPherson, Kathryn P.; Reed-Geaghan, Erin G.; Landreth, Gary E.; Anatomy and Cell Biology, School of Medicine
    Alzheimer's disease (AD) is a prominent neurodegenerative disorder characterized by deposition of β-amyloid (Aβ)-containing extracellular plaques, accompanied by a microglial-mediated inflammatory response, that leads to cognitive decline. Microglia perform many disease-modifying functions such as phagocytosis of plaques, plaque compaction, and modulation of inflammation through the secretion of cytokines. Microglia are reliant upon colony-stimulating factor receptor-1 (CSF1R) activation for survival. In AD mouse models, chronic targeted depletion of microglia via CSF1R antagonism attenuates plaque formation in early disease but fails to alter plaque burden in late disease. It is unclear if acute depletion of microglia during the peak period of plaque deposition will alter disease pathogenesis, and if so, whether these effects are reversible upon microglial repopulation. To test this, we administered the CSF1R antagonist PLX5622 to the 5XFAD mouse model of AD at four months of age for approximately one month. In a subset of mice, the drug treatment was discontinued, and the mice were fed a control diet for an additional month. We evaluated plaque burden and composition, microgliosis, inflammatory marker expression, and neuritic dystrophy. In 5XFAD animals, CSF1R blockade for 28 days depleted microglia across brain regions by over 50%, suppressed microgliosis, and reduced plaque burden. In microglial-depleted AD animals, neuritic dystrophy was enhanced, and increased diffuse-like plaques and fewer compact-like plaques were observed. Removal of PLX5622 elicited microglial repopulation and subsequent plaque remodeling, resulting in more compact plaques predominating microglia-repopulated regions. We found that microglia limit diffuse plaques by maintaining compact-like plaque properties, thereby blocking the progression of neuritic dystrophy. Microglial repopulation reverses these effects. Collectively, we show that microglia are neuroprotective through maintenance of plaque compaction and morphologies during peak disease progression.
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    The MR1/MAIT cell axis reduces phagocytosis and dystrophic neurites in Alzheimer’s disease
    (Wiley, 2025-01-03) Johnson, Season K.; Ackley, Samantha; Warren, Jalyn; Brutkiewicz, Randy R.; Microbiology and Immunology, School of Medicine
    Background: Plaques are a hallmark feature of Alzheimer’s disease (AD). We found the loss of mucosal‐associated invariant T (MAIT) cells and its antigen‐presenting molecule MR1 caused a delay in plaque pathology development in AD mouse models. However, it remains unknown how this axis is impacting microglial response and dystrophic neurites. This study aims to understand the impact of MAIT cells and microglial MR1 in AD. Method: Brain tissue from various ages of 5XFAD mice and those that are MR1‐deficient (MR1KO), was analyzed for the presence of MAIT cells. Methoxy‐X04 was used to analyze the phagocytic capacity of microglia ± MR1. Immunofluorescent microscopic analysis of dystrophic neurites in the brain was performed with antibodies against microglia, Aβ, Lamp1, Ubiquitin, and nAPP. Result: Injection of Methoxy‐X04 in 5XFAD and 5XFAD/MR1KO mice revealed reduced levels of Methoxy‐X04 uptake in CD11b+CD45low cells in the MR1 KO group (P < 0.05). However, this remained unaltered in the CD11b+CD45high cells. In the 5XFAD/MR1 KO group there was reduced expression of LAMP1, Ubiquitin, and nAPP in the hippocampus at 8 months compared to 5XFAD mice (P < 0.001). In the cortex only nAPP remained reduced in the 5XFAD/MR1 KO mice (P < 0.001). Conclusion: The loss of MR1 and MAIT cells reduced the phagocytic capacity of microglia and dystrophic neurite formation in the hippocampus. Our data indicate a potential detrimental role for MR1 and/or MAIT cells in AD pathology. Understanding this axis of the innate immune system could provide new clues as to the overall role of innate immunity in AD and its potential as a therapeutic target in AD.