6-Hydroxydopamine induces thymocyte apoptosis in mice.

6-Hydroxydopamine (6-OHDA) induces degeneration of noradrenergic nerves and has been shown to alter the immune responses. In this study, intraperitoneal administration of 6-OHDA induces mouse thymus atrophy. The lowest levels of thymus weight and cell number were reached at days 3 and 5 in mice receiving 6-OHDA treatment; they gradually recovered thereafter. On flow cytometry analysis, the most substantial reductions were recorded for CD4+CD8+ thymocytes, although the numbers of other subpopulations, i.e. CD4+CD8-, CD4-CD8+ and CD4-CD8- cells were also reduced. DNA fragmentation, a characteristic of apoptosis, was detected in the thymocytes following 6-OHDA injection. Pretreatment with desipramine greatly blocked the reduction in thymus size and thymocyte number, the changes in thymocyte subpopulations, the percentage of subdiploid (apoptotic) cells and the appearance of DNA fragmented bands. Furthermore, 6-OHDA-induced thymocyte apoptosis could also be detected in vitro, and was blocked by desipramine treatment. These results indicate that 6-OHDA induces mouse thymocytes to undergo apoptosis both in vivo and in vitro, and this effect is inhibited by catecholamine uptake blocker.