Estrogen and Selective Estrogen Receptor Modulators exert neuroprotective effects and stimulate the expression of seladin-1, a recently discovered anti-apoptotic gene, in human neuroblast long-term cell cultures.

According to the fact that Alzheimer’s disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. Experimental studies, still mostly performed using animal models, demonstrated that estrogen exerts neuroprotective effects. We previously established neuroblast long-term cell cultures fromhumanfetal olfactory epithelium. In the present study, we addressed the role of estrogen in these unique human cells, which express both the estrogen receptor (ER)- and ER. We found that 17-estradiol (17E2) and the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen exerted neuroprotective effects, which were independent of cell proliferation, by increasing resistance against -amyloid-induced toxicity, with the exception of the highest concentrations of raloxifene (10 and 100 nM). In addition, 17E2 exposure protected from oxidative stress, reduced apoptosis, and increased the expression of the catalytic subunit of telomerase. Furthermore, we evaluated by quantitative real-time RT-PCR whether estrogen/SERMs modulate the expression of the recently discovered seladin-1 (selective AD indicator-1) gene, which exerts neuroprotective effects and is down-regulated in AD-vulnerable brain regions. 17E2 (100 pM to 100 nM) and SERMs (1 nM) significantly increased the amount of seladin-1mRNA.Conversely, 10 and 100 nM raloxifene reduced the expression of seladin-1. The effect of estrogen appears mainly mediated by ER because the selective ER agonist propylpyrazole-triol determined a much greater increase of seladin-1 expression than the ER agonist diarylpropionitrile. Our results add new evidence, using human neuronal cells, for a beneficial effect of estrogen in preventing neurodegenerative diseases and suggest for the first time that seladin-1 may mediate this effect. (J Clin Endocrinol Metab 90: 1775–1782, 2005)