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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amyloid beta-Peptides / toxicity*
-
Animals
-
Cell Death / drug effects
-
Cell Death / physiology
-
Estradiol / pharmacology
-
Estrogen Receptor alpha / metabolism
-
Estrogen Receptor beta / metabolism
-
Estrogens / pharmacology*
-
Glutamic Acid / metabolism
-
Hippocampus / drug effects
-
Hippocampus / pathology
-
Hippocampus / physiopathology*
-
Neuroglia / drug effects
-
Neuroglia / pathology
-
Neuroglia / physiology
-
Neurons / drug effects
-
Neurons / pathology
-
Neurons / physiology*
-
Neuroprotective Agents / pharmacology*
-
Peptide Fragments / toxicity*
-
Phenols / pharmacology
-
Pyrazoles / pharmacology
-
Rats, Sprague-Dawley
-
Synapses / drug effects
-
Synapses / pathology
-
Synapses / physiology*
-
Time Factors
-
Tissue Culture Techniques
Substances
-
Amyloid beta-Peptides
-
Estrogen Receptor alpha
-
Estrogen Receptor beta
-
Estrogens
-
Neuroprotective Agents
-
Peptide Fragments
-
Phenols
-
Pyrazoles
-
amyloid beta-protein (25-35)
-
4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
-
Glutamic Acid
-
Estradiol