17β-estradiol protects depletion of rat temporal cortex somatostatinergic system by β-amyloid

Estradiol prevents amyloid-beta peptide (A beta)-induced cell death through estrogen receptors (ERs) and modulates somatostatin (SRIF) responsiveness in the rat brain. As intracerebroventricular (ICV) A beta 25-35 administration reduces SRIFergic tone in the temporal cortex of ovariectomized (Ovx) rats, we asked whether 17 beta-estradiol (E2) treatment can restore the A beta 25-35 induced changes in SRIF content, SRIF receptor density and adenylyl cyclase (AC) activity, as well as if these effects are mediated by ERs. E2 treatment did not change A beta 25-35 levels in the temporal cortex, but partially restored the SRIFergic parameters affected by A beta insult and decreased cell death, which was correlated with Akt activation. The ER antagonist ICI 182,780 prevented the protective effect of E2 on sst2 levels, but did not modify SRIF levels. Furthermore, ICI 182,780 treatment further decreased sst2 protein and mRNA levels when administered alone to A beta 25-35-treated rats, suggesting that it may block the effects of endogenous estrogens. These findings indicate that E2 protects the temporal cortical SRIFergic system from A beta-induced depletion independently of AP accumulation. (C) 2006 Elsevier Inc. All rights reserved.