Role of astrocytes in the neuroprotective actions of 17β-estradiol and selective estrogen receptor modulators.
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.
Instituto Cajal, CSIC, E-28002 Madrid, Spain.
Estefania
E
Acaz-Fonseca
Instituto Cajal, CSIC, E-28002 Madrid, Spain.
Rebeca
R
Sanchez-Gonzalez
Departamento de Biología Celular, Facultad de Biología, Universidad Complutense de Madrid, E-28040 Madrid, Spain.
Iñigo
I
Azcoitia
Instituto Cajal, CSIC, E-28002 Madrid, Spain.
Maria Angeles
MA
Arevalo
Instituto Cajal, CSIC, E-28002 Madrid, Spain. Electronic address: lmgs@cajal.csic.es.
Luis M
LM
Garcia-Segura
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000378:metabolism*
D004967:Estrogens; D018696:Neuroprotective Agents; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D004958:Estradiol
Brain edema; Glutamate transporters; Neuroglobin; Neuroinflammation; Neurotrophic factors; Reactive astrocytes