신경세포, 성상교세포, 미세신경교세포에서의 glucocorticoid에 의한 세포특이적 유전자 발현과 신호전달계에 관한 연구

Abstract

In the brain, there are several different types of cells, such as neurons, astrocytes, oligodendrocytes and microglia. We are interested in the roles and mechanisms of neuron-to-glia interaction in stress responses and stress-related psychiatric disorders such as depression. In the present study, we investigated cell type-specific effects of glucocorticoid on cellular function and gene expression in different brain cells. Dexamethasone (DEX, 1 M), a synthetic glucocorticoid, was treated for 24 hours in HT-22, C6 and BV-2 cells. DEX treatment significantly reduced both cellular mRNA expression and extracellular protein release of brain-derived neurotrophic factor (BDNF) in HT-22 neurons. However, the mRNA expressions of BDNF and crystallin alpha B were markedly increased in C6 astrocytes. Lipopolysaccharide (LPS, 200 ng/ml)-induced NO release, nuclei translocation of NF-B, degradation of IB, and mRNA expression of TNF alpha in microglia, a well-known phenomenon presenting proinflammatory capacity of microglia, was suppressed by DEX treatment. These effects were reversed by glucocorticoid receptor antagonist RU486 (Mifepristone). Our results suggest that glucocorticoid might deteriorate neuronal survival and maintenance of function. Astrocytes and microglia might protect damaged neurons vulnerable to stress hormone, by providing BDNF to neurons and anti-neuroinflammatory effect, respectively. Taken together, we postulate the specific roles and the neuron-glia interaction of neurons, astrocytes and microglia in stress responses and stress-related psychiatric disorders such as depression.