In the present study. we investigated cell type-specific effects of glucocorticoid on cellular function and gene expression in different brain cells. Dexamethasone (DEX, ㎛), a synthetic glucocorticoid, was treated for 24 h in HT-22 neurons, C6 astrocytes and BV-2 microglial cells. DEX Irealment significantly increased cellular mRNA levels of crystallin alpha B in C6 astrocytes and the effects were reversed by glucocorticoid receptor (GR) antagonist RU486 (Mifepristone). Lipopolysaccharide (LPS, 200 ng/ml) -induced NO release, nuclei translocation of NF-κB, degradation of cytosol IκB, and mRNA expression of TNF-alpha in microglia, a well-known phenomenon presenting pro-inflammatory capacity of microglia, was suppressed by DEX treatment. These effects were reversed by RU486 treatment. Our results suggest that glucocorticoid might deteriorate neuronal survival and maintenance offunction. Astrocytes and microglia might protect damaged neurons vulnerable to stress hormone. Taken together, we postulate neuron-glia interaction and the specific roles of neurons, astrocytes, and microglia in stress responses and stress-related psychiatric disorders such as depression.