Hypoxia-Ischemia Induces DNA Synthesis without Cell Proliferation in Dying Neurons in Adult Rodent Brain

摘要: Recent studies suggest that postmitotic neurons can reenter the cell cycle as a prelude to apoptosis after brain injury. However, most dying do not pass G1/S-phase checkpoint resume DNA synthesis. The specific factors trigger abortive synthesis are characterized. Here we show combination of hypoxia and ischemia induces adult rodent indicated by incorporation bromodeoxyuridine (BrdU) expression transition markers. After hypoxia-ischemia, majority BrdU- neuronal nuclei (NeuN)-immunoreactive cells also terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-stained, suggesting they undergo apoptosis. BrdU+ neurons, labeled shortly persist for >5 d but eventually disappear 28 d. Before disappearing, these BrdU+/NeuN+/TUNEL+ express proliferating marker Ki67, lose G1-phase cyclin-dependent kinase (CDK) inhibitors p16INK4 p27Kip1 induction late CDK2 activity phosphorylation retinoblastoma protein. This contrasts kainic acid excitotoxicity traumatic injury, which produce TUNEL-positive without evidence or transition. These findings hypoxia-ischemia triggers apoptosis-associated in brain. Our data demonstration neurogenesis injury requires only BrdU uptake mature markers showing absence apoptotic Manipulating aberrant occurs with perhaps neurodegenerative diseases could promote survival neurogenesis.