Glucocorticoids Decrease Astrocyte Numbers by Reducing Glucocorticoid Receptor Expression In Vitro and In Vivo

  • Unemura Kazuhiro
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Kume Toshiaki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Kondo Minami
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Maeda Yuki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Izumi Yasuhiko
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Akaike Akinori
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

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Glucocorticoids are stress hormones released from the adrenal cortex and their concentration is controlled by the hypothalamic–pituitary–adrenal axis. In this study, we investigated the effect of glucocorticoids on the number of astrocytes and glucocorticoid receptor (GR) expression in vitro and in vivo. Proliferation of cultured astrocytes was reduced following treatment with corticosterone and dexamethasone for 72 h. Corticosterone and dexamethasone also reduced GR expression in astrocytes. RU486, a GR antagonist, inhibited the reduction in both astrocyte proliferation and GR expression. Furthermore, GR knockdown by siRNA inhibited astrocyte proliferation. We also examined the effect of excessive glucocorticoid release on GR expression and the number of astrocytes in vivo by administering adrenocorticotropic hormone to rats for 14 days. GR expression was reduced in the prefrontal cortex and hippocampus and the number of astrocytes was reduced in the frontal cortex. Overall, our results suggest that glucocorticoids decrease the number of astrocytes by reducing GR expression.

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