Effects of iron and inflammation on astrocytes functions

Abstract

Iron accumulation and inflammation are present in a variety of neurodegenerative diseases include Alzheimer's disease and Parkinson's disease. Nowadays it has not yet known what the specifically causes neurodegeneration. There is probably not one single, but several factor are important to describe the etiology of these diseases. In this study, ferric ammonium citrate, pro-inflammatory cytokines including interleukin 1β and tumor necrosis factor alpha and combined were investigated the altered astrocytes functions. The results showed that FAC and combination of cytokines were markedly induced intracellular iron accumulation, free iron and reactive oxygen species, while the proliferation was inhibited in the presence of combination. In addition, the results demonstrated that iron enriched astrocytes alters the genes expression profiles involved in iron homeostasis by increased the expression of iron importer and storage genes couple with decreased in iron exporter gene. According to this condition, the rearrangement of astrocytes cytoskeletons were observed in an alteration of intermediate filaments, GFAP and vimentin, which refer to an initially activated astrocytes. Moreover, the combination of FAC and cytokines was able to induce the expression of the inflammation response genes including IL-1β, IL-6 and TNF-a. At the same time, the presence of FAC and combination of cytokines were significantly increased cytokines levels including IL-1β, IL-6 and TNF-a and glutamate secretion compared to unexposed control cells. Taken together, these findings suggest that astrocytes in neurodegenerative disorders are oxidatively stressed due to their tendency to accumulate iron, express and release more of cytokines and glutamate that can be harmful to neuron.