27-Hydroxycholesterol impairs learning and memory ability via decreasing brain glucose uptake mediated by the gut microbiota - 11/11/23
Abstract |
Brain glucose hypometabolism is a significant manifestation of Alzheimer’s disease (AD). 27-hydroxycholesterol (27-OHC) and the gut microbiota have been recognized as factors possibly influencing the pathogenesis of AD. This study aimed to investigate the link between 27-OHC, the gut microbiota, and brain glucose uptake in AD. Here, 6-month-old male C57BL/6 J mice were treated with sterile water or antibiotic cocktails, with or without 27-OHC and/or 27-OHC synthetic enzyme CYP27A1 inhibitor anastrozole (ANS). The gut microbiota, brain glucose uptake levels, and memory ability were measured. We observed that 27-OHC altered microbiota composition, damaged brain tissue structures, decreased the 2-deoxy-2-[18 F] fluorodeoxyglucose (18F-FDG) uptake value, downregulated the gene expression of glucose transporter type 4 (GLUT4), reduced the colocalization of GLUT1/glial fibrillary acidic protein (GFAP) in the hippocampus, and impaired spatial memory. ANS reversed the effects of 27-OHC. The antibiotic-treated mice did not exhibit similar results after 27-OHC treatment. This study reveals a potential molecular mechanism wherein 27-OHC-induced memory impairment might be linked to reduced brain glucose uptake, mediated by the gut microbiota.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | 27-OHC affects gut microbiota composition and induces gut microbiota dysbiosis. |
• | 27-OHC decreases brain glucose uptake and induces memory impairment of mice. |
• | 27-OHC did not decrease brain glucose uptake in microbiota-depleted mice. |
• | GLUT1 and GLUT4 are important factors in the regulation of brain glucose uptake. |
Keywords : 27-Hydroxycholesterol, Brain glucose uptake, Gut microbiota, Learning and memory ability
Plan
Vol 168
Article 115649- décembre 2023 Retour au numéro
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