Neurotoxicity of A beta amyloid protein in vitro is not altered by calcium channel blockade

Neurobiol Aging. Jan-Feb 1995;16(1):5-10. doi: 10.1016/0197-4580(95)80002-9.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Calcium Channel Blockers / pharmacology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Cyclic AMP / pharmacology
  • Cyclic GMP / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hydrolysis
  • Immunohistochemistry
  • Ion Channel Gating / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Fixation
  • Trypsin

Substances

  • Amyloid beta-Peptides
  • Calcium Channel Blockers
  • Culture Media, Serum-Free
  • Cyclic AMP
  • Trypsin
  • Cyclic GMP