Early β-Amyloid-induced Synaptic Dysfunction Is Counteracted by Estrogen in Organotypic Hippocampal Cultures.

MERLO S, SPAMPINATO SF, CAPANI F, SORTINO MA.

Curr Alzheimer Res.

Bentham Science

Año: 2016

In the present study we set up a model of slow progression of neuronal injury by exposing organotypic hippocampal cultures to a low concentration of Amyloid â (25-35) peptide (Aâ, 2 ìM) to analyze the time-related effects of 17-â estradiol (17â-E2, 10 nM). Neuronal death occurs after 7 d and is prevented by addition of 17â-E2 24 h prior to, together with or 48 h after exposure to Aâ. This effect is mimicked by selective ERá agonist PPT (100 nM). Treatment with Aâ leads to early and transient (16-72 h) increase of pre- and post-synaptic proteins synaptophysin and PSD95, followed by a decrease coincident with neuronal death (7d), all prevented by 17â-E2. At 72 h of Aâ exposure, synaptic activity is increased, as by higher levels of glutamate and increased loading and unloading of FM 1-43-labeled synaptic vesicles. All these effects are also prevented by 17â-E2. These data point out beneficial effects of estrogen on early Aâ-induced synaptic disruption.