Samuel Rajendran Raphael

• In contrast to most other vertebrates, teleost fish exhibit an unparalleled capacity to generate new cells in both the intact and the injured adult brain. This dissertation is focused on the occurrence, the extent and the fate of aneuploid cells (genome-modified individual cells characterized by the loss or gain of whole chromosomes) generated in the teleostean brain. Aneuploidy is observed in 80% of the newly-generated cells of the adult brain, but occurs at a very low rate in liver tissue, as shown by metaphase chromosome spreads and flow-cytometric DNA content analysis. To further analyze this phenomenon, the mitotic machinery of adult brain cells was examined for chromosome segregation defects which showed lagging chromosomes at metaphase and anaphase, as well as micronuclei and anaphase bridges, in the intact adult brain. To identify the fate of aneuploid cells in the adult brain, the Sphase cell cycle marker 5-bromo-2-deoxyuridine (BrdU) was injected into the fish, which were kept for various postadministration survival times. In the 100- and 860-day BrdU survival periods, the rate of mitotic segregation defects was significantly reduced, compared to the 2h and the 30-day survival times. These findings suggest that a good portion of the cells with mitotic defects were eliminated, possibly by apoptotic cell death. The analysis of post BrdU administration survival times in Apteronotus leptorhynchus up to 860 days, and up to 203 days in Danio rerio, revealed that a significant proportion of cells which exhibit nuclear abnormalities after mitosis survived for the rest of the life of the fish. In conclusion, this thesis demonstrates the evidence of the generation and maintenance of aneuploid cells in the adult fish brain that arise through chromosome missegregation which is a widespread phenomenon in the teleostean central nervous system.