title: Bone marrow contributes simultaneously to different neural types in the central nervous system through different mechanisms of plasticity.
abstract: Many studies have reported the contribution of bone marrow-derived cells (BMDC) to the CNS, raising the possibility of using them as a new source to repair damaged brain tissue or restore neuronal function. This process has mainly been investigated in the cerebellum, in which a degenerative  microenvironment has been suggested to be responsible for its modulation. The present study further analyzes the contribution of BMDC to different neural types in other adult brain areas, under both physiological and neurodegenerative conditions, together with the mechanisms of plasticity  involved. We grafted genetically marked green fluorescent protein/Cre bone marrow in irradiated recipients: a) the PCD (Purkinje Cell Degeneration) mutant mice, suffering a degeneration of specific neuronal populations at different ages, and b) their corresponding healthy controls.  These mice carried the conditional lacZ reporter gene to allow the identification of cell fusion events. Our results demonstrate that BMDC mainly generate microglial cells, although to a lesser extent a clear formation of neuronal types also exists. This neuronal recruitment was not  increased by the neurodegenerative processes occurring in PCD mice, where BMDC did not contribute to rescuing the degenerated neuronal populations either. However, an increase in the number of bone marrow-derived microglia was found along the life span in both experimental groups. Six weeks  after transplantation more bone marrow-derived microglial cells were observed in the olfactory bulb of the PCD mice compared to the control animals, where the degeneration of mitral cells was in process. In contrast, this difference was not observed in the cerebellum, where Purkinje cell degeneration  had been completed. These findings demonstrated that the degree of neurodegenerative environment can foster the recruitment of neural elements derived from bone marrow, but also provide the first evidence that BMDC can contribute simultaneously to different encephalic areas through different  mechanisms of plasticity: cell fusion for Purkinje cells and differentiation for olfactory bulb interneurons.
authors.affiliation: Laboratory of Neuronal Plasticity and Neurorepair, Institute for Neuroscience of Castilla y León, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Javier S
authors.initials: JS
authors.lastname: Recio
authors.forename: Manuel
authors.initials: M
authors.lastname: Álvarez-Dolado
authors.forename: David
authors.initials: D
authors.lastname: Díaz
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Baltanás
authors.forename: Marina
authors.initials: M
authors.lastname: Piquer-Gil
authors.forename: José R
authors.initials: JR
authors.lastname: Alonso
authors.forename: Eduardo
authors.initials: E
authors.lastname: Weruaga
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation; D002490:Central Nervous System / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000473:pathology; D008856:Microscopy, Fluorescence; D009410:Nerve Degeneration / Q000473:pathology / Q000628:therapy; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000473:pathology*
chemical_list: D049452:Green Fluorescent Proteins