Role of astrocytes in the neuroprotective actions of 17β-estradiol and selective estrogen receptor modulators

• Estradiol regulates reactive astrogliosis and the inflammatory response of astrocytes.
• Estradiol regulates neuroglobin expression in astrocytes.
• Estradiol regulates the synthesis of neurotrophic factors in astrocytes.
• Estradiol controls edema by regulating aquaporin 4 expression in astrocytes.
• Estradiol controls excitotoxicity by regulating glutamate transport by astrocytes.

Neuroprotective actions of 17β-estradiol (estradiol) are in part mediated by direct actions on neurons. Astrocytes, which play an essential role in the maintenance of the homeostasis of neural tissue, express estrogen receptors and are also involved in the neuroprotective actions of estradiol in the brain. Estradiol controls gliosis and regulates neuroinflammation, edema and glutamate transport acting on astrocytes. In addition, the hormone regulates the release of neurotrophic factors and other neuroprotective molecules by astrocytes. In addition, reactive astrocytes are a local source of neuroprotective estradiol for the injured brain. Since estradiol therapy is not free from peripheral risks, alternatives for the hormone have been explored. Some selective estrogen receptor modulators (SERMs), which are already in use in clinical practice for the treatment of breast cancer, osteoporosis or menopausal symptoms, exert similar actions to estradiol on astrocytes. Therefore, SERMs represent therapeutic alternatives to estradiol for the activation of astroglia-mediated neuroprotective mechanisms.