Differential Expression of Microglial BDNF in Response to Acute Hyperglycemia and Hypoxia

Abstract

Diabetes is one of the most common chronic disorders that affects the homeostasis of several systems including the central nervous system (CNS). Hyperglycemia, main feature of diabetes, is involved in pathogenesis of diabetic neuropathy. In addition, hyperglycemia increases mitochondrial oxygen consumption which leads to hypoxia and affects the neuronal survival, adversely. Brain‐derived neurotrophic (BDNF) is well known as neuroprotective factor which supports the survival of the neurons in the CNS. We hypothesize that microglial BDNF has a protective role against acute hyperglycemia and hypoxia. The objective of this study is to investigate the expression of BDNF in response to hyperglycemia and hypoxia. Murine microglial cell line BV‐2 cultured in Dulbecco's Modified Eagle Medium were used to investigate the effects of increased concentrations (30, 60, 90, 120 mM) at different durations (4, 8, 24 hours) on the viability of microglial cells. In addition, the effects of hypoxia on the survival rate of these cells was also assessed. Gene and protein expression of microglial BDNF was examined in response to increased concentrations of glucose and hypoxia as well as hypoxia inducible factor (HIF1‐alpha). Increased concentrations of glucose produced significant increase in gene expression of microglial BDNF and this response was concentration‐dependent (p < 0.001). On the other hand, gene expression of microglial BDNF was significantly decreased in response to hypoxia (4, 8, 24 hours) and this response was associated with reduced expression of HIF‐1 alpha (p < 0.05). In conclusion, the outcomes of this study demonstrated that expression of microglial BDNF was sensitive to increased concentration of glucose and decreased levels of oxygen. Further investigation will dissect the signaling pathways that are involved in this differential expression to gain a better understanding of the protective role of microglial BDNF against glucose and oxygen variability.