title: Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon.
abstract: The zebrafish has recently become a source of new data on the mechanisms of neural stem cell (NSC) maintenance and ongoing neurogenesis in adult brains. In this vertebrate, neurogenesis occurs at high levels in all ventricular regions of the brain, and brain injuries recover successfully, owing to the recruitment of radial glia, which function as NSCs. This new vertebrate model of adult neurogenesis is thus advancing our knowledge of the molecular cues in use for the activation of NSCs and fate of their progeny. Because the regenerative potential of somatic stem cells generally weakens with increasing age, it is important to assess the extent to which zebrafish NSC potential decreases or remains unaltered with age. We found that neurogenesis in the ventricular zone, in the olfactory bulb, and in a newly identified parenchymal zone of the telencephalon indeed declines as the fish ages and that oligodendrogenesis also declines. In the ventricular zone, the radial glial cell population remains largely unaltered morphologically but enters less frequently into the cell cycle and hence produces fewer neuroblasts. The neuroblasts themselves do not change their behavior with age and produce the same number of postmitotic neurons. Thus, decreased neurogenesis in the physiologically aging zebrafish brain is correlated with an increasing quiescence of radial glia. After injuries, radial glia in aged brains are reactivated, and the percentage of cell cycle entry is increased in the radial glia population. However, this reaction is far less pronounced than in younger animals, pointing to irreversible changes in aging zebrafish radial glia.
authors.affiliation: Sensory Biology and Organogenesis, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Edelmann
authors.forename: Lena
authors.initials: L
authors.lastname: Glashauser
authors.forename: Susanne
authors.initials: S
authors.lastname: Sprungala
authors.forename: Birgit
authors.initials: B
authors.lastname: Hesl
authors.forename: Maike
authors.initials: M
authors.lastname: Fritschle
authors.forename: Jovica
authors.initials: J
authors.lastname: Ninkovic
authors.forename: Leanne
authors.initials: L
authors.lastname: Godinho
authors.forename: Prisca
authors.initials: P
authors.lastname: Chapouton
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D030801:Animals, Genetically Modified; D001930:Brain Injuries / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism; D000067778:ELAV-Like Protein 3; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013687:Telencephalon / Q000473:pathology*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; D006657:Histones; D009419:Nerve Tissue Proteins; D018809:Proliferating Cell Nuclear Antigen; D064568:S100 Calcium Binding Protein beta Subunit; D029961:Zebrafish Proteins; C088635:elavl3 protein, zebrafish; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine
keywords: S100β; adult neurogenesis; aging; deltaA; gfap; injury; neural stem cells; quiescence; radial glia; regeneration; telencephalon; zebrafish