Is neurogenesis in the brain regulated by neurogenesis in the nose?

Abstract

Background: There is continuing neurogenesis in the subventricular zone (SVZ) of the adult brain which supplies interneurons to the olfactory bulb. There is also continuing neurogenesis in the olfactory epithelium (OE) supplying new olfactory sensory neurons whose axons terminate in the olfactory bulb. These axons synapse with tyrosine hydroxylase-positive periglomerular neurons, which are the product of subventricular zone neurogenesis. Hypothesis: SVZ neurogenesis is regulated coordinately with olfactory epithelial neurogenesis. Aims: The aim is to quantify the rate of cell proliferation in the SVZ after killing the olfactory sensory neurons, which upregulates neurogenesis in the OE. Methods: Adult mice were treated with methimazole, and the tissues were examined at different times after treatment. The survival of the olfactory sensory neurons within the OE was assessed together with their terminals within glomeruli of the olfactory bulb. The loss of tyrosine hydroxylase periglomerular neurons was quantified. Cell proliferation in the SVZ was also quantified using an antibody to Ki67, a marker of proliferating cells. Results: Methimazole treatment led to loss of olfactory sensory neurons in the OE, loss of their terminals in the glomeruli and loss of tyrosine-hydroxylase-positive periglomerular neurons in the olfactory bulb 14-18 days later. Cell proliferation in the SVZ was increased after methimazole treatment. Conclusion: The results are consistent with our hypothesis that neurogenesis in the brain may be regulated with neurogenesis in the nose. We propose the presence of a signalling pathway between these two neurogenic zones, which remains to be elucidated.