Idebenone protects hippocampal neurons against amyloid beta-peptide-induced neurotoxicity in rat primary cultures.
The application of amyloid beta-peptide (Abeta) 1-40 (10 microM) caused neurodegeneration of hippocampal neuronal cells, as indicated by the release of lactate dehydrogenase (LDH) into the culture medium. Treatment with idebenone (10-1000 nM), a potent antioxidant in mitochondria, protected the hippocampal neurons against the Abeta1-40(10 microM)-induced neurotoxicity. To determine the morphological change in neurons during the Abeta1-40-induced cytotoxicity, the cells were immunostained with anti-MAP2 antibodies. After 4-day exposure to 10 microM Abeta1-40, the number of neurons was reduced, and the surviving neurons had an apparently reduced number of neurites which were shorter than those of control neurons. When idebenone was added to the culture medium with Abeta1-40, the number of surviving neurons was significantly increased, and their neurites were as long as seen in control culture. These results suggest that reactive oxygen species mediate neurotoxicity of Abeta1-40, and idebenone protects neurons against the Abeta1-40-induced neurotoxicity.
Hirai
K
K
Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Osaka, Japan.
Hayako
H
H
Kato
K
K
Miyamoto
M
M
D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014451:Ubiquinone / Q000031:analogs & derivatives
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D016227:Benzoquinones; D014451:Ubiquinone; D007770:L-Lactate Dehydrogenase; C036619:idebenone