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The Journal of Neuroscience, September 12, 2007, 27(37):9885-9892; doi:10.1523/JNEUROSCI.2539-07.2007

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Development/Plasticity/Repair
Induction and Survival of Binucleated Purkinje Neurons by Selective Damage and Aging

Lorenzo Magrassi,^1 * Piercesare Grimaldi,^3 * Adalberto Ibatici,⁴ Mirko Corselli,⁴ Laura Ciardelli,² Sandra Castello,⁴ Marina Podestà,⁴ Francesco Frassoni,⁴ and Ferdinando Rossi³

¹Neurochirurgia Dipartimento Scienze Chirurgiche, Università di Pavia, Fondazione Instituto di Ricovero e Curaio a Carattere Scientifico Policlinico S. Matteo and Instituto di Geneticamolecolare Consiglio Nazionale delle Ricerche, and ²Laboratorio Immunologia Neonatale, Laboratorio Sperimentale di Ricerca Area trapiantologica, Fondazione Instituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, 27100 Pavia, Italy, ³Rita Levi Montalcini Center for Brain Repair, National Institute of Neuroscience, Dipartmento di Neuroscienze, Sez. di Fisiologia, Università di Torino, I-10125 Torino, Italy, and ⁴Centro Cellule Staminali e Terapia Cellulare, Divisione di Ematologia, Ospedale San Martino, 16100 Genova, Italy

Correspondence should be addressed to Dr. Lorenzo Magrassi, Neurosurgery, Department of Surgical Sciences, University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy. Email: magrassi{at}igm.cnr.it

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.

Key words: Purkinje neurons; bone marrow transplantation; cell fusion; brain repair; heterokaryons; cerebellum

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Received Feb. 3, 2007; revised July 12, 2007; accepted July 16, 2007.

Correspondence should be addressed to Dr. Lorenzo Magrassi, Neurosurgery, Department of Surgical Sciences, University of Pavia, Piazzale Golgi 2, 27100 Pavia, Italy. Email: magrassi{at}igm.cnr.it

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