Different fibrillar Abeta 1-42 concentrations induce adult hippocampal neurons to reenter various phases of the cell cycle.
In Alzheimer's disease (AD) cell cycle reentry precedes neuronal death, which could be induced by many cytotoxic factors. It is believed that beta amyloid (Abeta), the major component of extracellular plaques in AD, is potent in inducing neurons to reenter cell cycle. In AD brains, neurons expressing cell cycle markers are reported in many brain regions without any plaque formation, although very low levels of Abeta may still be detected. In the other side, because cell cycle reentry is not an immediate cause of apoptosis, neurons may remain in cell cycle phases for some time prior to their final death. In this study we examined if very low concentrations of Abeta 1-42 (picomolar) can trigger the adult neurons to reenter the cell cycle, and the effect of different Abeta concentrations on neuronal progression through different cell cycle phases. Primary adult neurons were treated with Abeta 1-42 at 2 x 10(-6), 2 x 10(-5), 2 x 10(-4), 0.5 and 2.5 microM concentrations. Cyclin D1 and cyclin B1 (the markers for G1 and G2 phases of the cell cycle, respectively) and apoptosis were assessed. Treatment with Abeta at 2.5 microM induced apoptosis. At lower levels however, Abeta promoted neurons entering G1 and G2 phases without apoptosis, with 0.5 microM of Abeta inducing neurons into G2, and 2 x 10(-5,) 2 x 10(-4) into G1 phases. Our results suggested that lower concentrations of Abeta induced neurons to reenter the cell cycle, and different concentrations had differential abilities to promote neurons into various cell cycle phases or trigger their death.
Department of Physiology, Shiraz University of Medical Sciences, Shiraz, Iran. majdsh@sums.ac.ir
Shohreh
S
Majd
Asadollah
A
Zarifkar
Karim
K
Rastegar
Mohammad Ali
MA
Takhshid
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats
D016229:Amyloid beta-Peptides; C534701:Ccnb1 protein, rat; D019926:Cyclin B; D056744:Cyclin B1; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D019938:Cyclin D1