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Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song
Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song
Arts & Sciences Electronic Theses and Dissertations
Carriers of the R47H allele of the microglia-specific lipid receptor TREM2 have a greatly increased risk of developing Alzheimerճ disease. The objective of this dissertation is to develop further mechanistic knowledge about how TREM2 is regulated and how TREM2 mutations affect microglia and neurodegeneration. Using an in vitro reporter assay, we find that several AD risk-associated TREM2 mutations decrease ligand-dependent activation. Using humanized TREM2 mice, we find that in vivo, the R47H mutation leads to reduced microglia activation and response to A_, as well as decreased shedding of soluble TREM2. These results suggest that TREM2 is protective during disease. We …
Regulation Of Neuroinflammation After Ischemic Stroke By Astroglial Endothelin Receptor Type-B Signaling, John Mcinnis
Regulation Of Neuroinflammation After Ischemic Stroke By Astroglial Endothelin Receptor Type-B Signaling, John Mcinnis
Graduate College Dissertations and Theses
A large body of neuroscientific research has focused on reactive gliosis and glial scar formation because these are among the most prominent features of the cellular response to central nervous system (CNS) injury. Despite much progress in our understanding, controversy remains regarding the relative balance between the protective nature of the astroglial scar and its anti-regenerative features. Recent work suggests that astrocytes are heterogeneous in their resting state and in their reactivity. In traumatic injuries such as stroke and spinal cord injury, proliferative reactive astrocytes protect CNS tissue. By contrast, under neuroinflammatory and/or neurodegenerative conditions, neurotoxic astrocyte phenotypes may contribute …