Neurotoxicity of A beta amyloid protein in vitro is not altered by calcium channel blockade.
In cortical cultures, A beta protein destabilizes calcium homeostasis, but direct neurotoxicity of A beta is not observed. In hippocampal cultures, we and others find treatment with A beta protein decreases neuronal survival, but the mechanism of neurotoxicity is unknown. We have used low-density, serum-free cultures of hippocampal neurons to determine whether the neurotoxicity of A beta protein in vitro can be altered by voltage- or ligand-gated calcium channel antagonists or cyclic nucleotides. In these cultures, neither omega-conotoxin, nifedipine, verapamil, APV, nor MK-801 altered the survival of neurons exposed to synthetic A beta 1-40. The N-channel antagonist diltiazem decreased A beta 1-40 toxicity repeatedly, but slightly, perhaps by indirectly contributing to increased neuronal viability. Treatment of cultures with dibutyryl cAMP, 8-bromo cAMP, dibutyryl cGMP, and 8-bromo cGMP also failed to alter A beta toxicity. Thus, the toxicity of beta protein in low-density hippocampal cultures was not directly altered either by calcium channel blockers or by the addition of cyclic nucleotides.
Whitson
J S
JS
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Appel
S H
SH
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis; D007150:Immunohistochemistry; D015640:Ion Channel Gating / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016707:Tissue Fixation; D014357:Trypsin
D016229:Amyloid beta-Peptides; D002121:Calcium Channel Blockers; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP; D014357:Trypsin; D006152:Cyclic GMP