Browsing by Author "Wirt, Ryan A."

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    Reduction in GABAB on glia induce Alzheimer's disease related changes
    (Elsevier, 2023) Leisgang Osse, Amanda M.; Pandey, Ravi S.; Wirt, Ryan A.; Ortiz, Andrew A.; Salazar, Arnold; Kimmich, Michael; Strom, Erin N.; Oblak, Adrian; Lamb, Bruce; Hyman, James M.; Carter, Gregory W.; Kinney, Jefferson; Radiology and Imaging Sciences, School of Medicine
    Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques (Aβ), neurofibrillary tangles (NFT), and neuroinflammation. Data have demonstrated that neuroinflammation contributes to Aβ and NFT onset and progression, indicating inflammation and glial signaling is vital to understanding AD. A previous investigation demonstrated a significant decrease of the GABAB receptor (GABABR) in APP/PS1 mice (Salazar et al., 2021). To determine if changes in GABABR restricted to glia serve a role in AD, we developed a mouse model with a reduction of GABABR restricted to macrophages, GAB/CX3ert. This model exhibits changes in gene expression and electrophysiological alterations similar to amyloid mouse models of AD. Crossing the GAB/CX3ert mouse with APP/PS1 resulted in significant increases in Aβ pathology. Our data demonstrates that decreased GABABR on macrophages leads to several changes observed in AD mouse models, as well as exacerbation of AD pathology when crossed with existing models. These data suggest a novel mechanism in AD pathogenesis.