Beta-estradiol attenuate amyloid beta-peptide toxicity via nicotinic receptors.
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.
Svensson
A L
AL
NEUROTEC, Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research, Huddinge University Hospital, Sweden.
Nordberg
A
A
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005562:Formazans; D006801:Humans; D008464:Mecamylamine / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D016716:PC12 Cells; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013778:Tetrazolium Salts; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002800:Cholinesterase Inhibitors; D005562:Formazans; D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D013778:Tetrazolium Salts; C054634:methyllycaconitine; C079782:MTT formazan; D004958:Estradiol; D008464:Mecamylamine; D009538:Nicotine; C082748:epibatidine; D000157:Aconitine