title: Adult neurogenesis restores dopaminergic neuronal loss in the olfactory bulb.
abstract: Subventricular zone (SVZ) neurogenesis continuously provides new GABA- and dopamine (DA)-containing interneurons for the olfactory bulb (OB) in most adult mammals. DAergic interneurons are located in the glomerular layer (GL) where they participate in the processing of sensory inputs. To examine whether adult neurogenesis might contribute to regeneration after circuit injury in mice, we induce DAergic neuronal loss by injecting 6-hydroxydopamine (6-OHDA) in the dorsal GL or in the right substantia nigra pars compacta. We found that a 6-OHDA treatment of the OB produces olfactory deficits and local inflammation and partially decreases the number of neurons expressing the enzyme tyrosine hydroxylase (TH) near the injected site. Blockade of inflammation by minocycline treatment immediately after the 6-OHDA administration rescued neither TH(+) interneuron number nor the olfactory deficits, suggesting that the olfactory impairments are most likely linked to TH(+) cell death and not to microglial activation. TH(+) interneuron number was restored 1 month later. This rescue resulted at least in part from enhanced recruitment of immature neurons targeting the lesioned GL area. Seven days after 6-OHDA lesion in the OB, we found that the integration of lentivirus-labeled adult-born neurons was biased: newly formed neurons were preferentially incorporated into glomerular circuits of the lesioned area. Behavioral rehabilitation occurs 2 months after lesion. This study establishes a new model into which loss of DAergic cells could be compensated by recruiting newly formed neurons. We propose that adult neurogenesis not only replenishes the population of DAergic bulbar neurons but that it also restores olfactory sensory processing.
authors.affiliation: Institut Pasteur, Laboratory for Perception and Memory, F-75015 Paris, France, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3571, F-75015 Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Lazarini
authors.affiliation: Institut Pasteur, Laboratory for Perception and Memory, F-75015 Paris, France, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3571, F-75015 Paris, France.
authors.forename: Marie-Madeleine
authors.initials: MM
authors.lastname: Gabellec
authors.affiliation: Institut Pasteur, Laboratory for Perception and Memory, F-75015 Paris, France, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3571, F-75015 Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Moigneu
authors.affiliation: Institut Pasteur, Unité d'Analyse d'Images Quantitative, F-75015 Paris, France, and Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, F-75015 Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: de Chaumont
authors.affiliation: Institut Pasteur, Unité d'Analyse d'Images Quantitative, F-75015 Paris, France, and Centre National de la Recherche Scientifique, Unité de Recherche Associée 2582, F-75015 Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Olivo-Marin
authors.affiliation: Institut Pasteur, Laboratory for Perception and Memory, F-75015 Paris, France, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3571, F-75015 Paris, France, pmlledo@pasteur.fr.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Lledo
mesh_terms: D000367:Age Factors; D000818:Animals; D059290:Dopaminergic Neurons / Q000473:pathology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000502:physiology*; D009830:Olfactory Bulb / Q000473:pathology* / Q000502:physiology*; D012903:Smell / Q000502:physiology*
keywords: Parkinson's disease; adult neural stem cell; innate responses; interneuron; microglia; regenerative medicine