title: Why Cortical Neurons Cannot Divide, and Why Do They Usually Die in the Attempt?
abstract: Cortical neurons are prime examples of terminally differentiated, postmitotic cells. However, under experimental or pathological conditions, they can re-enter the cell cycle and replicate DNA but are unable to divide, dying by apoptosis or becoming either polyploid or aneuploid. Any cellular state that depends on the action of genes and their products can be reverted or bypassed by spontaneous or induced mutations, yet there are currently no reports of dividing cortical neurons. Thus, it seems unlikely that the remarkably stable postmitotic condition of cortical neurons depends on specific gene functions. This Review summarizes evidence that the postmitotic state of cortical neurons depends on the high stability of its underlying nuclear structure that results from an entropy-driven process aimed at dissipating the intrinsic structural stress present in chromosomal DNA in such a way that the structural stability of the neuronal nucleus becomes an insurmountable energy barrier for karyokinesis and mitosis. From this perspective, the integral properties of the nuclear higher order structure in neurons provide an explanation not only for why cortical neurons cannot divide but also for why they usually die if they happen to replicate their DNA. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Laboratorio de Biología Molecular y Neurociencias, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca, Estado México, México.
authors.forename: Armando
authors.initials: A
authors.lastname: Aranda-Anzaldo
authors.affiliation: Laboratorio de Biología Molecular y Neurociencias, Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca, Estado México, México.
authors.forename: Myrna A R
authors.initials: MA
authors.lastname: Dent
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology*; D004247:DNA / Q000378:metabolism; D004261:DNA Replication / Q000502:physiology; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*
chemical_list: D004247:DNA
keywords: DNA replication; DNA supercoiling; cancer; entropy; nuclear matrix; tensegrity