Alterations in expression of the neurotrophic factors glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and brain-derived neurotrophic factor, in the target-deprived olfactory neuroepithelium

Abstract

Neuronal growth factors play an important role in the development and maintenance of the nervous system. In the olfactory system, neurogenesis and synapse formation occur not only during development but throughout life and it would be expected that growth factors play a significant role in these ongoing processes. We have examined the expression of three neurotrophic factors, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor and brain-derived neurotrophic factor in the normal rat olfactory system and following synaptic target ablation (olfactory bulbectomy). We found that brain-derived neurotrophic factor immunoreactivity was confined to the horizontal basal cells of the olfactory neuroepithelium and was unaltered by bulbectomy. Glial cell line-derived neurotrophic factor immunoreactivity was present in the mature olfactory neurons and also their synaptic target cells in the olfactory bulb. Following bulbectomy, glial cell line-derived neurotrophic factor immunoreactivity was abolished from the neuroepithelium. Ciliary neurotrophic factor was present throughout the olfactory neuronal lineage with strongest immunoreactivity in the horizontal basal cells and mature olfactory neurons as well as several cell types in the olfactory bulb. Postbulbectomy, there was loss of strong ciliary neurotrophic factor immunoreactivity in olfactory neurons, however, low levels persisted in the remaining neuronal population. Horizontal basal cell immunoreactivity persisted over three months. Our results would be consistent with glial cell line-derived neurotrophic factor expression in mature olfactory neurons being dependent upon functional synaptic contact with the olfactory bulb. Alternatively, this factor may be acting as target-derived growth factor for olfactory neurons, a role in keeping with its function in spinal motoneurons and in the nigrostriatal system. Brain-derived neurotrophic factor is implicated in the trophic support of immature neurons. Ciliary neurotrophic factor is clearly important in this unique neuronal system but elucidation of its role awaits further investigation.