Cell cycle reentry triggers hyperploidization and synaptic dysfunction followed by delayed cell death in differentiated cortical neurons.

ABSTRACT: Cell cycle reentry followed by neuronal hyperploidy and synaptic failure are two early hallmarks of Alzheimer's disease (AD), however their functional connection remains unexplored. To address this question, we induced cell cycle reentry in cultured cortical neurons by expressing SV40 large T antigen. Cell cycle reentry was followed by hyperploidy in ~70% of cortical neurons, and led to progressive axon initial segment loss and reduced density of dendritic PSD-95 puncta, which correlated with diminished spike generation and reduced spontaneous synaptic activity. This manipulation also resulted in delayed cell death, as previously observed in AD-affected hyperploid neurons. Membrane depolarization by high extracellular potassium maintained PSD-95 puncta density and partially rescued both sp

SUBMITTER: Barrio-Alonso E 

PROVIDER: S-EPMC6156334 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature