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Glucocorticoids—potent modulators of astrocytic calcium signaling
Author(s) -
Simard Marie,
Couldwell William T.,
Zhang Wei,
Song Hua,
Liu Shujun,
Cotrina Maria Luisa,
Goldman Steven,
Nedergaard Maiken
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(199910)28:1<1::aid-glia1>3.0.co;2-4
Subject(s) - glucocorticoid receptor , endocrinology , glucocorticoid , medicine , biology , methylprednisolone , calcium , agonist , astrocyte , receptor , calcium signaling , gap junction , microbiology and biotechnology , intracellular , central nervous system
Glucocorticoids are the first line of choice in the treatment of cerebral edema associated with brain tumors. High‐dose glucocorticoids reduce the extent of edema within hours, often relieving critical increases in intracranial pressure, but the mechanisms by which glucocorticoids modulate brain water content are not well‐understood. A possible target of action may be glucocorticoid receptor‐expressing astrocytes, which are the primary regulators of interstitial ion homeostasis in brain. In this study, we demonstrate that two glucocorticoids, methylprednisolone and dexamethasone, potentiate astrocytic signaling, via long‐range calcium waves. Glucocorticoid treatment increased both resting cytosolic calcium (Ca 2+ i ) level and the extent and amplitude of Ca 2+ wave propagation two‐fold, compared to matched controls. RU‐486, a potent steroid receptor antagonist, inhibited the effects of methylprednisolone. The glucocorticoid‐associated potentiation of Ca 2+ signaling may result from upregulation of the cellular ability to mobilize Ca 2+ and release ATP, because both agonist‐induced Ca 2+ i increments (via ATP and bradykinin) and ATP release were proportionally enhanced by glucocorticoids. In contrast, neither gap junction expression (as manifested connexin 43 immunoreactivity) nor functional coupling was significantly affected by methylprednisolone. Confocal microscopy revealed both the expression of glucocorticoid receptors and nuclear translocation of these receptors when exposed to methylprednisolone. We postulate that the edemolytic effects of glucocorticoids may result from enhanced astrocytic calcium signaling. GLIA 28:1–12, 1999. © 1999 Wiley‐Liss, Inc.