Abstract
A number of epidemiological studies suggest that estrogen therapy is linked to a reduced risk of developing Alzheimer's disease (AD). The present study was conducted to evaluate the effect of 17beta-estradiol on beta-amyloid (Abeta)-induced toxicity and was performed in rat pheochromocytoma PC 12 cells by measuring the mitochondrial activity. 17Beta-estradiol (10(-5), 10(-6) and 10(-8) M) attenuated Abeta(25-35)-induced toxicity in PC 12 cells. The neuroprotective effect of 17beta-estradiol (10(-5) M) was prevented in the presence of the nicotinic antagonists methyllycaconitine (MLA) and mecamylamine, suggesting an interaction probably via the alpha7 nicotinic receptor subtype. Chronic treatment with 17beta-estradiol (10(-10)-10(-5) M) alone did not change the number of [3H]epibatidine binding sites in human neuroblastoma SH-SY5Y cells and rat PC 12 cells, but significantly prevented the enhanced [3H]epibatidine binding in nicotine-treated PC 12 cells. This study demonstrates that 17beta-estradiol exerts neuroprotective effects which might involve interaction with the alpha7 nicotinic receptor subtype.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aconitine / analogs & derivatives
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Aconitine / pharmacology
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / toxicity*
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Animals
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Binding Sites / drug effects
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Bridged Bicyclo Compounds, Heterocyclic / antagonists & inhibitors
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Bridged Bicyclo Compounds, Heterocyclic / metabolism
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Cell Survival / drug effects
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Cholinesterase Inhibitors / pharmacology
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Estradiol / pharmacology*
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Formazans
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Humans
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Mecamylamine / pharmacology
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Neurons / cytology
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Neurons / drug effects*
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Neurons / metabolism
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Neuroprotective Agents / pharmacology*
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Nicotine / agonists
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Nicotine / antagonists & inhibitors
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Nicotine / pharmacology
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Nicotinic Agonists / pharmacology
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Nicotinic Antagonists / pharmacology
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PC12 Cells
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Pyridines / antagonists & inhibitors
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Pyridines / metabolism
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Rats
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Receptors, Nicotinic / metabolism*
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Tetrazolium Salts
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Tumor Cells, Cultured
Substances
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Amyloid beta-Peptides
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Bridged Bicyclo Compounds, Heterocyclic
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Cholinesterase Inhibitors
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Formazans
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Neuroprotective Agents
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Nicotinic Agonists
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Nicotinic Antagonists
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Pyridines
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Receptors, Nicotinic
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Tetrazolium Salts
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methyllycaconitine
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MTT formazan
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Estradiol
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Mecamylamine
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Nicotine
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epibatidine
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Aconitine