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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-07-0294v1 198/1/219    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tapia-Gonzalez, S. Articles by Diz-Chaves, Y. Search for Related Content PubMed PubMed Citation Articles by Tapia-Gonzalez, S. Articles by Diz-Chaves, Y.

S Tapia-Gonzalez, Instituto Cajal CSIC, Madrid, Spain
P Carrero, Instituto Cajal CSIC, Madrid, Spain
O Pernia, Instituto Cajal CSIC, Madrid, Spain
L Garcia-Segura, Instituto Cajal CSIC, Madrid, Spain
Y Diz-Chaves, Instituto Cajal CSIC, Madrid, Spain

Correspondence: Luis Garcia-Segura, Email: lmgs{at}cajal.csic.es

Abstract

It has been previously reported that the neuroprotective hormone oestradiol reduces microglia inflammatory activity. The objective of this study was to test whether two selective oestrogen receptor modulators, tamoxifen and raloxifene, modulate in vivo the activation of microglia induced by the peripheral administration of lipopolysaccharide. Activation of microglia was assessed in the white matter of the cerebellum using immunoreactivity for Major Histocompatability Complex-II. Oestradiol, tamoxifen and raloxifene decreased microglia activation induced by lipopolysaccharide in male and ovariectomized female rats, although the doses of oestradiol that were effective in decreasing microglia reactivity were not the same in both sexes. Tamoxifen reduced microglia activation in all experimental groups at all doses tested (0.5-2 mg/Kg. b.w.) while raloxifene loosed its anti-inflammatory activity at the higher dose tested (2 mg/Kg b.w.). In addition raloxifene had per se a moderate pro-inflammatory activity in the brain of control female rats and its anti-inflammatory activity was partially impaired in female animals after 1 month of deprivation of ovarian hormones. Spots of oestrogen receptor immunoreactivity were detected in the soma and cell processes of microglia. Treatment with lipopolysaccharide, oestradiol or tamoxifen induced an increase of oestrogen receptor immunoreactive spots in the perikaryon of microglia, while oestradiol antagonized the effect of lipopolysaccharide. The results indicate that some oestrogenic compounds decrease brain inflammation by a mechanism that may involve oestrogen receptors expressed by microglia. The findings support the potential therapeutic role of oestrogenic compounds as protective anti-inflammatory agents for the central nervous system.