Protective action of 17β‐estradiol and tamoxifen on glutamate toxicity in glial cells

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Abstract
Estrogens influence differentiation, growth and function of neurons, but less is known of their effects on glia. In our experiments reported here, the ovarian steroid, 17β-estradiol, and the “designer”, non-steroidal estrogen, tamoxifen, effectively protected C-6 glioma 2B clone cells from the cytotoxicity of the excitatory neurotransmitter, glutamate. Exposure of these cells to 10–20 mM glutamate induced 61–78% cell death. Pre-treatment of the cells with 0.01 mM estradiol or with 2 μM tamoxifen significantly reduced the glutamate-induced cell death, estradiol being the most effective in this regard. Estradiol- or tamoxifen-treated cells that had survived glutamate damage appeared more mature than controls. Thus, estrogens often used in therapy (estradiol as replacement after menopause and tamoxifen for treatment/prevention of breast cancer) may significantly protect glial cells against glutamate toxicity and stimulate cell differentiation.
Funding Information
  • BioTime, Inc., Berkeley, CA