Neuronal regeneration in the cerebellum of adult teleost fish, Apteronotus leptorhynchus: guidance of migrating young cells by radial glia.

In contrast to mammals, adult fish exhibit an enormous potential to replace injured brain neurons by newly generated ones. In the present study, the role of radial glia, identified by immunostaining against fibrillary acidic protein (GFAP), was examined in this process of neuronal regeneration. Approximately 8 days after application of a mechanical lesion to the corpus cerebelli in the teleost fish Apteronotus leptorhynchus, the areal density of radial glial fibers increased markedly in the ipsilateral dorsal molecular layer compared to shorter survival times, or to the densities found in the intact brain or in the hemisphere contralateral to the lesion. This density remained elevated throughout the time period of up to 100 days examined. The increase in fiber density was followed approximately 2 days later by a rise in the areal density of young cells, characterized by labeling with the nuclear dye DAPI, in the ipsilateral dorsal molecular layer. Based on this remarkable spatio-temporal correlation, and the frequently observed close apposition of elongated young cells to radial glial fibers, we hypothesize that radial glia play an important role in the guidance of migrating young cells from their proliferation zones to the site of lesion where regeneration takes place.

Radial glia-mediated up-regulation of somatostatin in the regenerating adult fish brain.

Adult teleost fish, Apteronotus leptorhynchus, exhibit an enormous regenerative capability after application of mechanical lesions to the dorsalmost subdivision of the cerebellum, the corpus cerebelli. Restoration of the neural tissue is achieved by a cascade of processes, including the guidance of migrating new neurons to the site of injury by radial glial fibers. These fibers are characterised by the expression of immunoreactive glial fibrillary acidic protein and by several morphological features. Within 12 h following the lesion, the fraction of radial glial fibers expressing the neuropeptide somatostatin (SRIF) dramatically increased from approximately 1%, as found in the intact brain, to roughly 27% 12-24 h post-lesion. Subsequently, the percentage of SRIF-expressing radial glial fibers gradually declined, until it reached background levels at about 10 days following the injury. We hypothesise that the expression of SRIF is related to the generation and/or differentiation of the new neurons produced in response to the lesion, rather than to the later guidance of these cells along their migratory pathway.