title: Induction and survival of binucleated Purkinje neurons by selective damage and aging.
abstract: 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.
authors.affiliation: Neurochirurgia Dipartimento Scienze Chirurgiche, Università di Pavia, Fondazione Instituto di Ricovero e Curaio a Carattere Scientifico Policlinico S. Matteo, 27100 Pavia, Italy. magrassi@igm.cnr.it
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Magrassi
authors.forename: Piercesare
authors.initials: P
authors.lastname: Grimaldi
authors.forename: Adalberto
authors.initials: A
authors.lastname: Ibatici
authors.forename: Mirko
authors.initials: M
authors.lastname: Corselli
authors.forename: Laura
authors.initials: L
authors.lastname: Ciardelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Castello
authors.forename: Marina
authors.initials: M
authors.lastname: Podestà
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D002459:Cell Fusion / Q000379:methods; D002467:Cell Nucleus / Q000502:physiology*; D048750:Cell Nucleus Division / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley