Title

Fructose-derived advanced glycation end products (AGEs) enhance neuroinflammation and alter immune function in the brain

Document Type

Conference Proceeding

Publication Date

3-2013

Abstract

Objective: Microglia are the primary immune cells of the central nervous system and can cause neuronal damage and death through the creation of a sustained inflammatory response via proinflammatory cytokines and reactive oxygen species (ROS). Microglia become activated in response to neuronal damage and noxious stimuli, including advanced glycation end products (AGEs). AGEs form naturally in the body when free sugars react with proteins. The objective of this study is to examine effects of AGEs on the activation and cell death of microglial cells in vitro. Fructose-derived AGEs were used in this study because fructose is more reactive than glucose and may produce more toxic products. The increased levels of fructose in the human diet also make these end products of clinical interest.

Methods:Fructose-AGEs were prepared by incubating fructose with bovine serum albumin (BSA) at 37°C for 8 weeks. An immortalized microglial cell line (HAPI) was subjected to physiologic concentrations of fructose-AGE in vitro. Effects on microglia are measured via changes in inflammatory gene expression, cell death, and the production of cytokines, nitric oxide, and ROS. Statistically significant changes for each measure were determined using one-way ANOVA with a Bonferroni post-hoc test; P

Results: Research in progress. Preliminary results reveal fructose-AGEs at physiologically relevant doses are capable of reducing microglial viability by as much as 20% and doubling nitric oxide production compared with controls. Gene expression analysis revealed significant increases in proinflammatory cytokine production (tumor necrosis factor-alpha and macrophage colony-stimulating factor) in a dose-dependent manner. Measurements of ROS are ongoing and will be completed in the upcoming months. Implications of this study are that the ability of fructose-AGEs to activate and kill microglial cells may help elucidate the pathology of many neurodegenerative diseases. The prevention of their formation or induced damage should be investigated as a target for neurologic diseases.

DOI

https://doi.org/10.1331/JAPhA.2013.13508

Comments

Presented at the American Pharmacists Association Annual Meeting in Los Angeles, California, March 2013.

The abstract was published in the Journal of the American Pharmacists Association, March–April, 2013. Volume 53, Issue 2, Page e115: https://doi.org/10.1331/JAPhA.2013.13508

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