Estrogen suppresses the impact of glucose deprivation on astrocytic calcium levels and signaling independently of the nuclear estrogen receptor

Glucose deprivation of astrocytes results in an elevation of cytosolic calcium concentration ([Ca2+]i) [Kahlert, S., Reiser, G., 2000. Requirement of glycolytic and mitochondrial energy supply for loading of Ca2+ stores and InsP3-mediated Ca2+ signaling in rat hippocampus astrocytes. J. Neurosci. Res. 61, 409-420; Silver, I.A., Deas, J., Erecinska, M., 1997. Ion homeostasis in brain cells: differences in intracellular ion responses to energy limitation between cultured neurons and glial cells. Neuroscience 78, 589-601] equivalent to an impairment of astrocytic energy metabolism and function. Superfusion of fura-2 loaded primary cortical astrocytes with glucose-free solution triggered a slow and progressive, 56-fold increase of the [Ca2+]i from 60 nM up to 3.3 μM within 2 h. Re-addition of glucose led to a rapid drop of [Ca2+]i, yet [Ca2+]i did not fully recover to the low levels recorded prior to glucose deprivation and, moreover, astrocytic Ca2+ signaling was impaired: adenosine 5′-triphosphate (ATP) and uridine 5′-triphosphate (UTP) were no longer able to trigger a transient Ca2+ response as recorded in controls. 17β-estradiol protected astrocytes from the glucose deprivation-induced [Ca2+]i increase and the impaired signaling independently of the nuclear estrogen receptor, as the antiestrogen tamoxifen and the protein synthesis inhibitor cycloheximide did not impede the protective effect of 17β-estradiol.