Induction and survival of binucleated Purkinje neurons by selective damage and aging.

Fusion of bone marrow-derived cells with adult Purkinje cells in the cerebellum gives rise to binucleated Purkinje cells. Whether fusion
can be modulated by epigenetic factors and whether fused neurons are stable has remained unclear. Here, we show that in mice and rats,
partial ablation of Purkinje cells and local microglial activation in the absence of structural damage to the cerebellum increase the rate of
fusion. Moreover, mouse Purkinje cells once fused with bone marrow-derived cells are viable for at least 7 months. We also show that
cerebellar irradiation is unnecessary for the generation of binucleated Purkinje cells after bone marrow grafting. Moreover, binucleated
Purkinje cells can be found in aged mice that did not receive any treatment, suggesting that fusion events occasionally occur throughout
the whole lifespan of healthy, unmanipulated individuals. However, in aged chimeric mice that, after bone marrow transplant, have the
majority of their nucleated blood cells fluorescent, the number of binucleated fluorescent Purkinje cells is two orders of magnitude less
than the total number of binucleated Purkinje cells. This suggests that, in the majority of heterokaryons, either the incoming nucleus is
quickly inactivated or fusion is not the only way to generate a binucleated Purkinje cell.