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.


CONCLUSIONS
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.
Espejel
Silvia
S
Department of Neurological Surgery, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA.
Romero
Ricardo
R
Alvarez-Buylla
Arturo
A
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation / Q000379:methods; D002066:Busulfan / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D002459:Cell Fusion / Q000379:methods; D002467:Cell Nucleus / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002531:Cerebellum / Q000166:cytology*; D004307:Dose-Response Relationship, Radiation; D004622:Embryo, Mammalian; D005697:Galactosides / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010320:Parvalbumins / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects*; D014916:Whole-Body Irradiation / Q000379:methods*
D005697:Galactosides; D007166:Immunosuppressive Agents; D007211:Indoles; D010320:Parvalbumins; D049452:Green Fluorescent Proteins; D002066:Busulfan; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside