Estradiol or genistein prevent Alzheimer's disease-associated inflammation correlating with an increase PPARI[sup3 expression in cultured astrocytes

• Published in: Brain research 2010-02, Vol.1312, p.138-144
• Main Authors: Valles, Soraya L, Dolz-Gaiton, Pablo, Gambini, Juan, Borras, Consuelo, LLoret, Ana, Pallardo, Federico V, Vina, Jose
• Format: Article
• Language: English
• ISSN: 0006-8993
• DOI: 10.1016/j.brainres.2009.11.044

Inflammation has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). The main inflammatory players in AD are the glial cells which initiate the inflammatory response. One of the earliest neuropathological changes in AD is the accumulation of astrocytes at sites of Ab deposition. It is desirable to find methods of tipping the balance towards anti-inflammatory state. Estrogenic compounds have shown anti-inflammatory and also antioxidant activity. Astrocytes were pretreated with 17-bestradiol or with genistein, and 48 h later treated with 5aaI14M amyloid beta (Ab) for 24 h. We found that Ab induces inflammatory mediators, such as cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin 1b (IL-1b) and tumor necrosis factor a (TNF-a). All these effects were prevented when cells were pretreated with estradiol or genistein, demonstrating anti-inflammatory effects of estradiol or genistein in astrocytes in primary culture. The Ab-stimulated expression of pro-inflammatory genes in cells is antagonized by the action of the PPARs (peroxisome proliferator activated receptors). Here we detected an increase in PPAR-I[sup3 expression in astrocytes in primary culture treated with Ab and estradiol or soy isoflavone genistein. Thus, some of the anti-inflammatory effects of estrogenic compounds may be mediated and activated by PPARs suppressing a diverse array of inflammatory responses caused by Ab in astrocytes in primary culture.