estrogen and inflammation

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Subject: Role of estrogen in neuroinflammation

Endocrinology. 2006 May;147(5):2263-72. Epub 2006 Feb 9. Related

Articles,

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The endogenous estrogen status regulates microglia reactivity in animal

models of neuroinflammation.

Vegeto E

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itoo\

l=pubmed_Abstract & term=%22Vegeto+E%22%5BAuthor%5D> , Belcredito S

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itoo\

l=pubmed_Abstract & term=%22Belcredito+S%22%5BAuthor%5D> , Ghisletti S

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itoo\

l=pubmed_Abstract & term=%22Ghisletti+S%22%5BAuthor%5D> , Meda C

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itoo\

l=pubmed_Abstract & term=%22Meda+C%22%5BAuthor%5D> , Etteri S

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itoo\

l=pubmed_Abstract & term=%22Etteri+S%22%5BAuthor%5D> , Maggi A

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itoo\

l=pubmed_Abstract & term=%22Maggi+A%22%5BAuthor%5D> .

Center of Excellence on Neurodegenerative Diseases and Department of

Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133

Milan, Italy. elisabetta.vegeto@....

It has been previously demonstrated that 17beta-estradiol (E(2))

inhibits the response of microglia, the resident brain macrophages, to

acute injuries in specific brain regions. We here show that the effect

of E(2) 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-alpha, 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 beta-amyloid (Abeta) deposits and facilitates

the progression of these cells toward a highly reactive state. Long-term

administration of E(2) 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 Abeta

deposits. Finally, we show that E(2) inhibits Abeta-induced expression

of scavenger receptor-A in macrophage cells, providing a mechanism for

the effect of E(2) on Abeta 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

PMID: 16469811 [PubMed - in process]