| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, 20133 Milan, Italy
Address all correspondence and requests for reprints to: Elisabetta Vegeto, Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy. E-mail: elisabetta.vegeto{at}unimi.it.
It has been previously demonstrated that 17ß-estradiol (E2) inhibits the response of microglia, the resident brain macrophages, to acute injuries in specific brain regions. We here show that the effect of E2 in acute brain inflammation is widespread and that the hormone reduces the expression of inflammatory mediators, such as monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and TNF-
, induced by lipopolysaccharide, demonstrating that microglia are a direct target of estrogen action in brain. Using the APP23 mice, an animal model of Alzheimer’s disease reproducing chronic neuroinflammation, we demonstrate that ovary ablation increases microglia activation at ß-amyloid (Aß) deposits and facilitates the progression of these cells toward a highly reactive state. Long-term administration of E2 reverts the effects of ovariectomy and decreases microglia reactivity compared with control animals. In this animal model, these events do not correlate with a reduced number of Aß deposits. Finally, we show that E2 inhibits Aß-induced expression of scavenger receptor-A in macrophage cells, providing a mechanism for the effect of E2 on Aß signaling observed in the APP23 mice. Altogether, our observations reveal a substantial involvement of endogenous estrogen in neuroinflammatory processes and provide novel mechanisms for hormone action in the brain.
This article has been cited by other articles:
 |
|
 |
|
  S. Tapia-Gonzalez, P. Carrero, O. Pernia, L. M Garcia-Segura, and Y. Diz-Chaves Selective oestrogen receptor (ER) modulators reduce microglia reactivity in vivo after peripheral inflammation: potential role of microglial ERs J. Endocrinol., July 1, 2008; 198(1): 219 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Tenenbaum, A. N. Azab, and J. Kaplanski Effects of estrogen against LPS-induced inflammation and toxicity in primary rat glial and neuronal cultures Innate Immunity, June 1, 2007; 13(3): 158 - 166. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Suzuki, C. M. Brown, C. D. Dela Cruz, E. Yang, D. A. Bridwell, and P. M. Wise Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions PNAS, April 3, 2007; 104(14): 6013 - 6018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L HARKONEN and H. K. VAANANEN Monocyte-Macrophage System as a Target for Estrogen and Selective Estrogen Receptor Modulators Ann. N.Y. Acad. Sci., November 1, 2006; 1089(1): 218 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. POZZI, V. BENEDUSI, A. MAGGI, and E. VEGETO Estrogen Action in Neuroprotection and Brain Inflammation Ann. N.Y. Acad. Sci., November 1, 2006; 1089(1): 302 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
