title: Bone marrow cell transplantation restores olfaction in the degenerated olfactory bulb.
abstract: Bone marrow contains heterogeneous cell types including end-lineage cells, committed tissue progenitors, and multipotent stem/progenitor cells. The immense plasticity of bone marrow cells allows them to populate diverse tissues such as the encephalon, and give rise to a variety of cell types. This unique plasticity makes bone marrow-derived cells good candidates for cell therapy aiming at restoring impaired brain circuits. In the present study, bone marrow cells were transplanted into P20 mice that exhibit selective olfactory degeneration in adulthood between P60 and P150. These animals, the so-called Purkinje Cell Degeneration (PCD) mutant mice, suffer from a progressive and specific loss of a subpopulation of principal neurons of the olfactory bulb, the mitral cells (MCs), sparing the other principal neurons, the tufted cells. As such, PCD mice constitute an interesting model to evaluate the specific role of MCs in olfaction and to test the restorative function of transplanted bone marrow-derived cells. Using precision olfactometry, we revealed that mutant mice lacking MCs exhibited a deficit in odorant detection and discrimination. Remarkably, the transplantation of wild-type bone marrow-derived cells into irradiated PCD mutant mice generated a large population of microglial cells in the olfactory bulb and reduced the degenerative process. The alleviation of MC loss in transplanted mice was accompanied by functional recovery witnessed by significantly improved olfactory detection and enhanced odor discrimination. Together, these data suggest that: (1) bone marrow-derived cells represent an effective neuroprotective tool to restore degenerative brain circuits, and (2) MCs are necessary to encode odor concentration and odor identity in the mouse olfactory bulb.
authors: Laboratory of Neuronal Plasticity and Neurorepair, Institute for Neuroscience of Castilla y León-INCyL and Universidad de Salamanca, E-37007 Salamanca, Spain.
authors: David
authors: D
authors: Díaz
authors: Gabriel
authors: G
authors: Lepousez
authors: Gilles
authors: G
authors: Gheusi
authors: José Ramón
authors: JR
authors: Alonso
authors: Pierre-Marie
authors: PM
authors: Lledo
authors: Eduardo
authors: E
authors: Weruaga
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D016026:Bone Marrow Transplantation / Q000379:methods*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D019922:GAP-43 Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000601:surgery*; D009812:Odorants; D009830:Olfactory Bulb / Q000473:pathology*; D051842:Olfactory Marker Protein / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology*; D012684:Sensory Thresholds / Q000502:physiology; D012903:Smell / Q000502:physiology*
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D019922:GAP-43 Protein; D008840:Microfilament Proteins; D051842:Olfactory Marker Protein; D049452:Green Fluorescent Proteins