Glucose and fructose directly stimulate brain-derived neurotrophic factor gene expression in microglia

Abstract

Brain-derived neurotrophic factor (BDNF) is expressed in both hypothalamic neurons and microglia, and plays a critical role in the regulation of metabolism. Although hypothalamic expression of BDNF is regulated by metabolic signals such as nutrients and hormones, it remains unknown whether these signals differentially regulate BDNF expression in different cell types. The present study aimed to determine whether glucose and fructose regulate BDNF expression in microglia via the specific glucose transporter. To determine the effect of glucose and fructose on Bdnf mRNA and protein expression, murine microglial cell line SIM-A9 cells were exposed to the maintenance concentration of glucose (17.5 mmol/l), high glucose (25 mmol/l), or fructose (7.5 mmol/l) for 40 min to 24 h. To determine whether the blockade of glucose transporter 5 (GLUT5) negates the effect of glucose on Bdnf mRNA expression, cells were exposed to 25 mmol/l glucose in the presence or absence of the GLUT5 inhibitor for 4 h. Levels of Bdnf mRNA and protein were measured by real-time PCR and ELISA, respectively. High glucose caused a significant increase in both pan-Bdnf and long-form Bdnf (L-Bdnf) mRNA as well as protein levels when compared with the maintenance of concentration of glucose in a time-dependent manner. Fructose treatment also increased L-Bdnf mRNA expression. Pharmacological blockade of GLUT5 did not affect glucose-induced Bdnf mRNA expression. These findings suggest that glucose and fructose directly stimulate Bdnf mRNA expression in microglia and these responses may mediate the metabolic actions of glucose and fructose.