Glucose Uptake in Pigment Glia Suppresses Tau-Induced Inflammation and Photoreceptor Degeneration

Authors

Mikiko Oka
Sho Nakajima
Emiko Suzuki
Shinya Yamamoto
Kanae Ando

Language

English

Publication Date

4-1-2025

Journal

Disease Models & Mechanisms

DOI

10.1242/dmm.052057

PMID

40151148

PMCID

PMC12067088

PubMedCentral® Posted Date

4-29-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Brain 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 a Drosophila model of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human MATP (hereafter referred to as Tau) in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by the formation of dark-stained round inclusion-like structures and swelling of the lamina cortex. We found that inclusion-like structures are formed by glial phagocytosis, and swelling of the laminal cortex correlates with the expression of antimicrobial peptides. Coexpression of human glucose transporter 3 (SLC2A3, hereafter referred to as GLUT3) with Tau in the retina does not affect Tau levels but suppresses these inflammatory responses and photoreceptor degeneration. We also found that expression of GLUT3, 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.

Keywords

Animals, Glucose, Neuroglia, tau Proteins, Retinal Degeneration, Inflammation, Humans, Drosophila melanogaster, Photoreceptor Cells, Invertebrate, Glucose Transporter Type 3, Phagocytosis, Alzheimer Disease, Drosophila Proteins, Disease Models, Animal, Photoreceptor Cells, Drosophila, Neurodegeneration, Glia, Inflammation, Glucose

Published Open-Access

yes

Recommended Citation

Oka, Mikiko; Nakajima, Sho; Suzuki, Emiko; et al., "Glucose Uptake in Pigment Glia Suppresses Tau-Induced Inflammation and Photoreceptor Degeneration" (2025). Duncan NRI Faculty and Staff Publications. 118.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/118