Dynamics of caspase-3-mediated apoptosis during spinal cord regeneration in the teleost fish, Apteronotus leptorhynchus

In contrast to mammals, adult teleost fish exhibit a vast potential for central nervous system regeneration after injury. Among other mechanisms, this capacity is mediated by replacement of cells lost to injury by new neurons and glia. Here, we examined the spatio-temporal dynamics of apoptosis, and its relationship to the generation and the differentiation of new cells, during this cell replacement phase. As an experimental paradigm, caudal transection of the spinal cord in the teleost fish Apteronotus leptorhynchus was used. During the cell replacement phase, there was a rather constant percentage of new cells (identified by incorporation of 5-bromo-2′-deoxyuridine into newly synthesized DNA) that underwent apoptosis (identified by anti-active caspase-3 immunolabeling). Many of these cells were also immunopositive for the marker proteins Hu C/D or glial fibrillary acidic protein, indicating that a large portion of cells undergo apoptosis after differentiation into neurons or glia, respectively. The spatial distribution of apoptotic cells was uneven, displaying a radial peak in the mid parenchymal regions and a longitudinal peak at the site of the initial spinal transection. The latter persisted for over 100 days post-injury, indicating possible problems in the integration of new cells at the interface between the old, intact tissue and the regenerated portion of the spinal cord. Taken together, the results of the present study are consistent with the hypothesis that apoptosis plays a role in the development of the new tissue during the cell replacement phase of the regenerating teleostean spinal cord.