SELECTIVE OESTROGEN RECEPTOR MODULATORS DECREASE THE INFLAMMATORY RESPONSE OF GLIAL CELLS.

AREVALO MA; DIZ-CHAVES Y; SANTOS-GALINDO M; BELLINI MJ; GARCIA-SEGURA LM

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Oxford; Año: 2012 vol. 24 p. 183 - 190

0953-8194

Neuroinflammation is a feature of many neurological disorders that is accompanied by the activation of glial cells and the release of proinflammatory cytokines and chemokines. Such activation is a normal response oriented to protect neural tissue and it is mainly regulated by microglia and astroglia. However, excessive and chronic activation of glia may lead to neurotoxicity and may be harmful for neural tissue. The ovarian hormone oestradiol exerts protective actions in the central nervous system that, at least in part, are mediated by a reduction of reactive gliosis. Several selective oestrogen receptor modulators may also exert neuroprotective effects by controlling glial inflammatory responses. Thus, tamoxifen and raloxifene decrease the inflammatory response caused by lipopolysaccharide, a bacterial endotoxin, in mouse and rat microglia cells in vitro. Tamoxifen and raloxifene are also able to reduce microglia activation in the brain of male and female rats in vivo after the peripheral administration of lipopolysaccharide. In addition, tamoxifen decreases microglia inflammatory response induced by irradiation. Furthermore, treatment with tamoxifen and raloxifene resulted in a significant reduction in the number of reactive astrocytes in the hippocampus of young, middle-aged and older female rats after a stab wound injury. Tamoxifen, raloxifene and the new selective oestrogen receptor modulators ospemifene and bazedoxifene decrease the expression and release of interleukine-6 and interferon-γ inducible protein-10 in cultured astrocytes exposed to lipopolysaccharide. Ospemifene and bazedoxifene exert anti-inflammatory effects in astrocytes by a mechanism involving classical oestrogen receptors and the inhibition of nuclear factor-kB p65 transactivation. These data suggest that oestrogenic compounds are candidates to counteract brain inflammation under neurodegenerative conditions by targeting the production and release of pro-inflammatory molecules by glial cells.