Glucose uptake in pigment glia suppresses tau-induced inflammation and photoreceptor degeneration inDrosophila

Abstract

SummaryBrain inflammation contributes to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using aDrosophilamodel of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human tau in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by inclusion formation and swelling of lamina glial cells. We found that inclusions are formed by glial phagocytosis, and swelling of the laminal cortex correlates with the expression of antimicrobial peptides (AMPs). Co-expression of human glucose transporter 3 (GLUT3) with tau in the retina does not affect tau levels but suppresses these inflammatory responses and photoreceptor degeneration. We also found that expression ofGLUT3, specifically in the pigment glia, is sufficient to suppress inflammatory phenotypes and mitigate photoreceptor degeneration in the tau-expressing retina. Our results suggest that glial glucose metabolism contributes to inflammatory responses and neurodegeneration in tauopathy.HighlightsTau expression in the fly retina induces glial activationPigment glial cells mediate inflammatory phenotypes in the degenerating retinaEnhanced glucose uptake in the pigment glia suppresses inflammation and photoreceptor neurodegeneration caused by tau expression