Enhanced Neurogenesis in the Olfactory Bulb in Adult Mice after Injury Induced by Acute Treatment with Trimethyltin

In adults, the subventricular zone is known to contain undifferentiated neural progenitor cells that proliferate and generate the olfactory bulb (GB) interneurons throughout life. We earlier showed that trimethyltin (TMT) causes neuronal damage in the granular cell layer of the GB in adult mice. In the current study, we examined neurogenesis in the GB in adult mice after injury induced by acute treatment with TMT. On day 2 post-TMT treatment, enhanced incorporation of 5-bromo-2'-deoxyuridine (BrdU) was seen in the granular cell layer of the OB. Many of the BrdU-labeled cells were undifferentiated cells on day 2 post-treatment. On day 30 post-TMT treatment, BrdU-labeled neuronal cells were dramatically increased in number in the granular cell layer of the OB. However, TMT treatment was ineffective in affecting the migration of BrdU-labeled cells from the subventricular zone to the OB. The results of a neurosphere assay revealed that the number of neurospheres derived from the GB was significantly increased on day 2 post-TMT treatment. The neurosphere-forming neural progenitor cells derived from the GB of TMT-treated animals were capable of differentiating into neuronal cells as well as into astrocytes. Taken together, our data suggest that the GB has the ability to undergo enhanced neurogenesis following TMT-induced neuronal injury in adult mice. (C) 2009 Wiley-Liss, Inc.