Radiation damage increases Purkinje neuron heterokaryons in neonatal cerebellum

Objective Recent studies have shown that in radiated and bone marrow transplanted mice, bone marrow‐derived cells (BMDCs) fuse with Purkinje neurons resulting in the formation of binucleated heterokaryons. Here we investigated whether radiation plays a role in the formation of Purkinje neuron heterokaryons. Methods Fused cells were identified by reporter gene expression in mice, carrying floxed LacZ (R26R‐LacZ) in all cells and Cre in hematopoietic‐derived cells. Cell fusion was confirmed by the presence of two nuclei. The number of fused Purkinje neurons was studied in: 1) whole‐body radiated newborn and adult R26R‐LacZ mice, transplanted with bone marrow cells expressing Cre; 2) in newborn and adult mice that received different doses of radiation to the head; and 3) in radiated and non‐radiated newborns treated with a myeloablative drug before bone marrow transplantation. Results In neonatal, but not in adult cerebelleum, radiation—in a dose‐dependent manner—induces a dramatic increase in the number of fused Purkinje neurons. Interpretation Increase recruitment of BMDCs into the cerebellum, radiation damage to cerebellar cells, or both, increase the formation of fused Purkinje cells. BMDC‐Purkinje heterokaryons formation may reflect an endogeneous neuronal repair mechanism, or it could be a by‐product of radiation‐induced inflammation. In either case, fused Purkinje neurons increase following radiation damage in the developing cerebellum. The above observations reveal a novel consequence of head radiation in neonatal rodents. It will be interesting to determine if similar increase in the number of binucleated Purkinje neurons, occurs in children that receive radiation during early development. Ann Neurol 2009;66:100–109