Cell division of neurons in an oxygen-glucose deprivation model

Abstract

Event Abstract Back to Event Cell division of neurons in an oxygen-glucose deprivation model Itsuki Ajioka1, 2* and Mio Oshikawa1 1 Tokyo Medical and Dental University (TMDU), Center for Brain Integration Research (CBIR), Japan 2 JST, PRESTO, Japan Although neurons are able to re-enter the cell cycle in pathological situations such as neurodegeneration and stroke, they are tightly protected from cell division and undergo cell death after S phase progression. Neurons become permanently post-mitotic immediately after cell cycle exit during development, however, the mechanism underlying non-dividing feature is mostly unknown. The Retinoblastoma protein family (Rb, p107, p130) plays a central role in preventing cells from entering the S phase. When Rb family expression is lost in neuronal progenitor cells, the subsequent coordination of cell-cycle exit and neuronal differentiation is lost, and neurons can divide in some cases such as retinoblastoma (Ajioka et al., 2007). We recently developed a technique for conditionally inactivating all of the Rb family members in mouse cortical progenitors, either before or immediately after cell-cycle exit, by electroporation with Cre-expressing plasmids containing a ubiquitous pCAG promoter or a neuron-specific pMAP2 promoter (Oshikawa et al., 2013). When the Rb family is inactivated using pCAG-Cre, immature neurons generated from the pCAG-induced Rb-TKO (Rb-/-; p107-/-; p130-/-) progenitors divide. In contrast, the pMAP2-induced Rb-TKO immature neurons enter the S phase, but undergo cell death. Thus, once progenitor daughter cells exit the cell-cycle and initiate neuronal differentiation, they are prevented from undergoing cell division, and maintain mitotic resistance even after acute Rb family inactivation. These findings led us to hypothesize that pathological neurons in the S phase undergo cell death by activating mitotic safeguards. To investigate whether such mitotic safeguard protects pathological neurons in the S phase from undergoing cell division, we used oxygen-glucose deprivation (OGD) model in which post-mitotic cortical neurons undergo cell death after S phase progression and Rb phosphorylation. We demonstrate the cell division of dying OGD neurons in the S phase by inactivating mitotic safeguards. Keywords: Cell Cycle, Cell Division, Phosphorylation, Neuron, retinoblastoma protein family Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Ajioka I and Oshikawa M (2016). Cell division of neurons in an oxygen-glucose deprivation model. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00182 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Prof. Itsuki Ajioka, Tokyo Medical and Dental University (TMDU), Center for Brain Integration Research (CBIR), Tokyo, Tokyo, Japan, iajioka.cbir@tmd.ac.jp Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Itsuki Ajioka Mio Oshikawa Google Itsuki Ajioka Mio Oshikawa Google Scholar Itsuki Ajioka Mio Oshikawa PubMed Itsuki Ajioka Mio Oshikawa Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.