Cell proliferation after lesions in the cerebellum of adult teleost fish: time course, origin, and type of new cells produced.

In contrast to mammals, fish exhibit an enormous capacity to replace damaged neurons following injuries to the adult central nervous system. As the mechanisms controlling this so-called neuronal regeneration are unknown, we have, in the present study, examined the role of cell proliferation in this process. Lesions were applied to one subdivision of the cerebellum, the corpus cerebelli, in the teleost fish Apteronotus leptorhynchus. Proliferative activity was monitored through incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine into replicating DNA. Cerebellar lesions induce high proliferative activity especially in areas in close vicinity to the injury, although the number of cells produced is also increased in other regions of the corpus cerebelli. Many of the cells generated in these areas become, after migration, specifically incorporated at the site of the lesion. The vast majority of them is dividing between 1 and 10 days following the lesion, with the maximum proliferative activity occurring at 5 days. Remarkably, also cells dividing 2 days prior to applying a lesion participate, at a significant number, in the regenerative process. Combination of 5-bromo-2'-deoxyuridine labeling with retrograde tract-tracing techniques demonstrated that at least some of the new cells that replace damaged neurons are cerebellar granule cells. This ability to generate new neurons, together with the previously described occurrence of apoptosis to remove damaged cells, is likely to form the basis for the enormous capacity of teleost fish to perform neuronal regeneration.