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The aim of the present study was to determine the effect of serum deprivation on primary microglia, BV-2 cells and primary astrocytes. Cell morphology combined with the expression of phospho-(p-)38 and p-extracellular signal-regulated kinase (ERK) were assessed. Serum deprivation resulted in various alterations in the three cell cultures. Primary microglia and BV-2 cells exhibited alterations indicative of activation under serum treatment, as well as lipopolysaccharide (LPS) treatment. However, astrocytes did not react as fast. Regarding