Increased radial glia quiescence, decreased reactivation upon injury and unaltered neuroblast behavior underlie decreased neurogenesis in the aging zebrafish telencephalon

• Published in: Journal of comparative neurology (1911) 2013-09, Vol.521 (13), p.3099-3115
• Main Authors: Edelmann, Kathrin, Glashauser, Lena, Sprungala, Susanne, Hesl, Birgit, Fritschle, Maike, Ninkovic, Jovica, Godinho, Leanne, Chapouton, Prisca
• Format: Article
• Language: English
• Subjects: adult neurogenesis; Age Factors; Aging; Animals; Animals, Genetically Modified; Brain Injuries - pathology; Bromodeoxyuridine - metabolism; Cell Count; Danio rerio; deltaA; Disease Models, Animal; ELAV Proteins - genetics; ELAV Proteins - metabolism; ELAV-Like Protein 3; Freshwater; gfap; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Histones - metabolism; injury; Nerve Regeneration - physiology; Nerve Tissue Proteins - metabolism; neural stem cells; Neural Stem Cells - physiology; Neuroglia - physiology; Proliferating Cell Nuclear Antigen - metabolism; quiescence; radial glia; regeneration; S100 Calcium Binding Protein beta Subunit - metabolism; S100β; telencephalon; Telencephalon - pathology; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.23347

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. J. Comp. Neurol. 521: 3099–3115, 2013. © 2013 Wiley Periodicals, Inc. In the adult zebrafish, radial glial cells (depicted in green and yellow on a cross section of the telencephalon) cover the ventricular area, on the outer surface and at the midline and span their process towards the pial surface. Divisions of the radial glia (yellow) and of their neuroblasts offsprings (yellow dots) are at the source of the newly born neurons (red dots). Mitotic activity of the radial glia diminishes with age and neurogenesis is reduced: compare the “old” right hemisphere.to the “young” left hemisphere. (The cells within the section are represented at a larger scale for the sake of simplicity).