IDEBENONE PROTECTS HIPPOCAMPAL-NEURONS AGAINST AMYLOID BETA-PEPTIDE-INDUCED NEUROTOXICITY IN RAT PRIMARY CULTURES

The application of amyloid beta-peptide (A beta) 1-40 (10 mu M) caused neurodegeneration of hippocampal neuronal cells, as indicated by the release of lactate dehydrogenase (LDH) into the culture medium. Treatm ent with idebenone (10-1000 nM), a potent antioxidant in mitochondria, protected the hippocampal neurons against the A beta 1-40 (10 mu M)-i nduced neurotoxicity. To determine the morphological change in neurons during; the A beta 1-40-induced cytotoxicity, the cells were immunost ained with anti-MAP2 antibodies. After 4-day exposure to 10 mu M A bet a 1-40, the number of neurons was reduced, and the surviving neurons h ad an apparently reduced number of neurites which were shorter than th ose of control neurons. When idebenone was added to the culture medium with A beta 1-40, the number of surviving neurons was significantly i ncreased, and their neurites were as long as seen in control culture. These results suggest that reactive oxygen species mediate neurotoxici ty of A beta 1-40, and idebenone protects neurons against the A beta 1 -40-induced neurotoxicity.