Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression

Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ER alpha and ER beta were involved in the protection by tibolone on GD cells, being ER beta preferentially involved on these actions over ERa. Tibolone increased viability of GD cells by a mechanism fully blocked by an ER beta antagonist and partially blocked by an ERa antagonist. Furthermore, ER beta inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondria] membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ER beta and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ER beta and the upregulation of neuroglobin. (C) 2016 Elsevier Ireland Ltd. All rights reserved.