Functional analysis of glucocorticoid treatment associated astrocyte-proteins

Stress induces various neurobiological changes related to neurodegenerative diseases or mental disorders, including elevated neuronal dysfunction, neurotransmitter degradation and turnover. Astrocytes regulate synapses bidirectionally as neuroprotective glia. While glucocorticoids are generally well studied, specific cellular mechanisms require further investigation. Neuronal dysfunction characterized by changes in glucocorticoid signaling is associated with changes in astrocytes; however, very little is known about the impact of glucocorticoids on astrocyte-specific cellular reactions. We have analyzed protein expression patterns following dexamethasone treatment of normal human astrocyte cultures. Protein analysis of cortical astrocyte cultures treated with dexamethasone for 48 h using LCMS/MS identified 3 unique proteins with ≥ twofold change in expression in the cell lysate and cell culture medium. Clustering analysis associated with these protein expression changes is known to be impacted by glucocorticoids. The upregulation of phosphoglycerate kinase and downregulation of pyruvate kinase strongly suggest a disrupted glycolytic process, which may hinder the astrocyte-neuron lactate shuttle critical for neuronal energy supply and cognitive function. Furthermore, the downregulation of insulin in the astrocyte culture medium indicates reduced insulin export from the astrocytes. These findings suggest that dexamethasone exposure has a pronounced effect on astrocyte metabolism and deploys astrocyte-specific patterns of regulatory responses to glucocorticoids and controls neuronal activation.