Sex steroids and neural survival

P. MANNELLA; A.M. SANCHEZ; M.S. GIRETTI; A. CARUSO; S. GARIBALDI; M. FLAMINI; X.D. FU; C. BALDACCI; A.R. GENAZZANI; T. SIMONCINI

8-11 March, Rome, Italy

Congreso; The 2nd World Congress on Gender-Specific Medicine and Ageing. The Endocrine Impact.; 2007

Sex steroids present several effects on the brain as protecting neural cells against toxic stimuli action. On the basis of these data, hormone replacement therapy (HRT) has been largely used in the past to restore an hormonal environment which protects brain from damages. However, last clinical trials have completely challenged these issues and nowadays HRT has been reconsidered. Several reasons have been raised to explain this discrepancy on HRT between basic science and evidence-based medicine. Accumulating evidence from basic science studies demonstrates that steroids exert profound protective actions against various forms of neurodegenerative diseases and injury. Although a thorough understanding of the mechanisms underlying the protective effect of estrogens is far from complete, significant progress has been achieved through the use of in vivo as well as in vitro models. Here we review the results from our laboratory demonstrating that steroids promotes neural cell survival and these effects depend on the timing of exposure and on the steroid preparation of neural cells. Indeed, we focus on the mechanism by which steroids promote survival in neural cells, via the activation of MAPK and PI3K pathways to the activation of Nitric Oxide Synthase (NOS). Definitely, the understanding of these processes represent the first step for the comprehension of steroid effects on the brain in order to prevent or, at least, delay neurodegenerative disease development as shown in the last clinical trials.