title: Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb.
abstract: In the adult rat olfactory bulb, neurons are continually generated from progenitors that reside in the lateral ventricle wall. This study investigates long-term survival and cell death of newly generated cells within the adult olfactory bulb. After injecting rats at 2 months of age with 5-bromodeoxyuridine (BrdU), the newly generated cells were quantified over a period of 19 months. A peak of BrdU-positive cells was reached in the olfactory bulb 1 month after BrdU injection, when all new cells have finished migrating from the ventricle wall. Thereafter, a reduction of BrdU-positive cells to about 50% was observed and it was confirmed by dUTP-nick end-labelling (TUNEL) that progenitors and young neurons undergo programmed cell death. However, cells that survived the first 3 months after BrdU injection persisted for up to 19 months. The majority of the BrdU-positive cells that reach the olfactory bulb differentiate into granule cells, but a small fraction migrate further into the glomerular layer. These newborn cells differentiate more slowly into periglomerular interneurons, with a delay of more than 1 month when compared to the granule cells. The newly generated periglomerular neurons, among them a significant fraction of dopaminergic cells, showed a similar decline in number compared to the granule cell layer and long-term survival for the remaining new neurons of up to 19 months. Rather than replacing old neurons, this data suggests that adult olfactory bulb neurogenesis utilizes the overproduction and turnover of young neurons, which is reminiscent of the cellular dynamics observed during brain development.
authors.affiliation: Department of Neurology, University of Regensburg, Universitätsstrasse 84, D- 93053 Regensburg, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Winner
authors.forename: Christiana M
authors.initials: CM
authors.lastname: Cooper-Kuhn
authors.forename: Robert
authors.initials: R
authors.lastname: Aigner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
authors.forename: H Georg
authors.initials: HG
authors.lastname: Kuhn
mesh_terms: D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D002470:Cell Survival; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D009830:Olfactory Bulb / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells; D013997:Time Factors
chemical_list: D001973:Bromodeoxyuridine