Although several lines of evidence have indicated that menopause is associated with increased susceptibility to neurological disorders, the mechanisms involved in this phenomenon remain to be elucidated. Because neuroinflammation is a common feature of a number of brain diseases, we hypothesized that the cessation of ovarian functions and the consequent decrease in estrogen receptor (ER)-mediated antiinflammatory activity may represent a trigger for postmenopausal brain dysfunctions. The aim of the present study was to investigate the effects of aging and surgical menopause on the activity of ER in neuroinflammation. The present study shows that ER genes are expressed in the hippocampus, but ER transcriptional activity decreases significantly beginning at 12 months of age in intact and ovariectomized mice. With ovariectomy, we observe an age-dependent accumulation of mRNA encoding inflammatory mediators (e.g. TNF alpha, IL1 beta, and macrophage inflammatory protein-2) and changes in the morphology of astroglia and microglia. In addition, we show that aging itself is coupled with an exaggerated response to acute inflammatory stimuli with a major accumulation of TNF alpha, IL1 beta, macrophage inflammatory protein-2, and macrophage chemoattractant protein-1 mRNA in response to lipopolysaccharide administration. The response to acute inflammatory stimuli appears to be differentially modulated by the duration of hormone deprivation in 12-month-old mice. Taken together, the present results show that aging is associated with decreased ER activity, despite continuous ER synthesis, and that age-dependent neuroinflammation is strongly influenced by hormone deprivation.
A Lack of Ovarian Function Increases Neuroinflammation in Aged Mice / V. Benedusi, C. Meda, S. Della Torre, G. Monteleone, E. Vegeto, A. Maggi. - In: ENDOCRINOLOGY. - ISSN 0013-7227. - 153:6(2012 Jun), pp. 2777-2788.
|Titolo:||A Lack of Ovarian Function Increases Neuroinflammation in Aged Mice|
BENEDUSI, VALERIA (Primo)
MEDA, CLARA (Secondo)
VEGETO, ELISABETTA (Penultimo)
MAGGI, ADRIANA CATERINA (Ultimo)
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||giu-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1210/en.2011-1925|
|Appare nelle tipologie:||01 - Articolo su periodico|