Proliferation, migration, neuronal differentiation, and long-term survival of new cells in the adult zebrafish brain

Abstract

In contrast to mammals, fish exhibit an enormous potential to produce new cells in the adult brain. By labeling mitotically dividing cells with 5-bromo-2'-deoxyuridine (BrdU), we have characterized the development of these cells in the zebrafish (Danio rerio). Proliferation zones were located in specific regions of the olfactory bulb, dorsal telencephalon (including a region presumably homologous to the mammalian hippocampus), preoptic area, dorsal zone of the periventricular hypothalamus, optic tectum, torus longitudinalis, vagal lobe, parenchyma near the rhombencephalic ventricle, and in a region of the medulla oblongata lateral to the vagal motor nucleus, as well as in all three subdivisions of the cerebellum, the valvula cerebelli, the corpus cerebelli, and the lobus caudalis cerebelli. In the valvula cerebelli and the corpus cerebelli, the young cells migrated from their site of origin in the molecular layers to the corresponding granule cell layers. By contrast, in the lobus caudalis cerebelli and optic tectum, no indication of a migration of the newly generated cells over wider distances could be obtained. BrdU-labeled cells remained present in the brain over at least 292 days post-BrdU administration, indicating a long-term survival of a significant portion of the newly generated cells. The combination of BrdU immunohistochemistry with immunolabeling against the neural marker protein Hu, or with retrograde tracing, suggested a neuronal differentiation in a large portion of the young cells.

Upregulation of anti-apoptotic factors in upper motor neurons after spinal cord injury in adult zebrafish

“…2 and 3). Our data were in good agreement with previous findings in the adult zebrafish brain, reporting that the number of newly-generated neurons is extremely low in the region where descending neurons exist (Zupanc et al, 2005;Hinsch and Zupanc, 2007). In contrast to the upper motor neurons in the brainstem, motor neurons in the spinal cord become apoptotic after SCI, and neurogenesis from the ependymal zone around the central canal is activated via sonic hedgehog and/or Notch signaling (Reimer et al, 2008;Reimer et al, 2009;Dias et al, 2012).…”

Polysialyltransferase expression is linked to neuronal migration in the developing and adult zebrafish

“…These findings suggest that PST and STX activity could act in an individual or synergistic manner in the adult CNS. Their expression is confined to many regions of adult neurogenesis and neuronal migration, which occurs more widespread in zebrafish than in higher vertebrates (Zupanc et al, 2005;Adolf et al, 2006;Grandel et al, 2006). For example, pst and stx expression is found in the subpallial stripe, the zebrafish equivalent of the mammalian RMS (Adolf et al, 2006) and in other ventricular regions such as in the periventricular gray zone of the optic tectum or the hypothalamus.…”

“…Moreover, in contrast to mammals, adult zebrafish show significant levels of neurogenesis in almost all regions of the adult brain and have a pronounced capability to regenerate CNS lesions (Becker et al, 2004;Zupanc et al, 2005;Zupanc and Zupanc, 2006;Adolf et al, 2006;Grandel et al, 2006). For example, stab wounds in the adult zebrafish cerebellum are repaired within several days by an up-regulation of neurogenesis in the cerebellar molecular layer followed by directed migration of these neuronal progenitors toward the lesion site (Liu et al, 2004;Zupanc and Zupanc, 2006).…”

Stretching the limits: Stem cells in regeneration science

“…These new cells originate from pluripotent adult stem cells harbored in dozens of specific proliferation zones within the brain (Hinsch and Zupanc, 2006). Approximately half of the new cells persist for the rest of the fish's life and develop into a variety of cell types, including neurons and glial cells (Zupanc et al, 1996(Zupanc et al, , 2005Ott et al, 1997;Hinsch and Zupanc, 2007).…”