Reduction in Aβ‐induced cell death in the hippocampus of 17β‐estradiol‐treated female rats is associated with an increase in IGF‐I signaling and somatostatinergic tone

Several studies indicate that 17β‐estradiol (E2) protects against amyloid β‐peptide (Aβ)‐induced cell death and activates factors associated with learning and memory, a function involving the hippocampal somatostatinergic system. As alterations in somatostatin have been demonstrated in Alzheimer′s disease, we examined whether E2 prevents changes in the hippocampal somatostatinergic system induced by Aβ25‐35 and cell death, as well as the possible involvement of leptin and insulin‐like growth factor (IGF)‐I signaling. We also measured the levels of Aβ proteases neprilysin and insulin‐degrading‐enzyme. Co‐administration of E2 with Aβ25‐35 reduced both its levels and cell death, in addition to preventing the Aβ‐induced depletion of some somatostatinergic parameters. Activation of leptin and IGF‐I pathways increased after E2 co‐administration, and this correlated with changes in the somatostatinergic system. Changes in some components of this system were inversely related with Aβ levels and cell death. Moreover, neprilysin levels were increased only in Aβ plus E2‐treated rats and E2 prevented the Aβ‐induced insulin‐degrading‐enzyme reduction. Our results suggest that the E2‐induced reduction in cell death is related to lower Aβ levels, probably because of IGF‐I and somatostatin modulation of Aβ proteases. We asked how 17β‐estradiol (E2) protects against β‐amyloid (Aβ)‐induced cell death. E2 co‐administration prevents Aβ‐produced depletion of hippocampal somatostatin (SRIF) by an IGF‐I‐mediated mechanism, being related this protective effect with an increase in Aβ proteases. Our results suggest that the E2‐induced reduction in cell death is related to lower Aβ levels, probably because of SRIF modulation of Aβ proteases. CREB, cAMP response element‐binding protein; IGF‐I, insulin‐like growth factor‐I; STAT3, signal transducer and activator of transcription‐3. We asked how 17β‐estradiol (E2) protects against β‐amyloid (Aβ)‐induced cell death. E2 co‐administration prevents Aβ‐produced depletion of hippocampal somatostatin (SRIF) by an IGF‐I‐mediated mechanism, being related this protective effect with an increase in Aβ proteases. Our results suggest that the E2‐induced reduction in cell death is related to lower Aβ levels, probably because of SRIF modulation of Aβ proteases. CREB, cAMP response element‐binding protein; IGF‐I, insulin‐like growth factor‐I; STAT3, signal transducer and activator of transcription‐3.