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

Author(s): Sara Merlo , Simona Federica Spampinato , Francisco Capani , Maria Angela Sortino .

Journal Name: Current Alzheimer Research

Volume 13 , Issue 6 , 2016

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Abstract:

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 β (25-35) peptide (Aβ, 2 μM) to analyze the time-related effects of 17-β estradiol (17β-E2, 10 nM). Neuronal death occurs after 7 d and is prevented by addition of 17β-E2 24 h prior to, together with or 48 h after exposure to Aβ. This effect is mimicked by selective ERα agonist PPT (100 nM). Treatment with Aβ 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 17β-E2. At 72 h of Aβ 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 17β-E2. These data point out beneficial effects of estrogen on early Aβ-induced synaptic disruption.

Keywords: 17β-estradiol, Alzheimer’s Disease, estrogen receptor α, synaptic hyperactivity, synaptophysin.

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Article Details

VOLUME: 13
ISSUE: 6
Year: 2016
Page: [631 - 640]
Pages: 10
DOI: 10.2174/1567205013666160125113509
Price: $58

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