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Full-Text Articles in Neuroscience and Neurobiology
Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan
Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan
School of Medicine Faculty Publications
Aims: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells-2; TREM2) regulates the production of pro- and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect. Methods: We used 2 hours of the MCAo model in rats and intravenously administered DHA or vehicle at 3 hours after the onset of MCAo. Neurobehavioral assessment was performed on days 1, 3, 7, and 14; …
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 …