Neurotrophic factors regulate neuronal differentiation, as well as cell survival and proliferation.1  A lack of neurotrophic support can result in cell death and atrophy of surviving neurons and their processes.12 Studies of rabbit and rat olfactory systems have shown that removal of the olfactory epithelium causes degeneration of some neurons in the olfactory bulbs.13   Additional studies of young rodents indicate that depriving the olfactory bulbs of active nerve input by naris occlusion results in reduced bulb size.8   Restricting olfactory nerve activity by naris occlusion also results in increased levels of cell death in the olfactory bulbs.14 It has recently been shown that neurotrophins can be released from the neurons, which synthesize them in an activity-dependent manner.15  Since neurotrophins can be released from neurons during stimulation, and some olfactory bulb neurons can die from a lack of olfactory nerve stimulation, it may be that neurotrophic factors are transported to the bulb and released by active olfactory nerve afferents.  Cell death in the deprived olfactory bulb therefore may be due to a lack of trophic support from the olfactory nerve.

This study demonstrates that neurotrophins are expressed by the developing rat olfactory epithelium, and NT3 immunoreactivity can be detected in olfactory nerve axons. Neurotrophin receptors are expressed in the developing forebrain and olfactory bulb.   Based on our results, we propose that, as has been seen in other parts of the brain, there is anterograde transport of neurotrophins in the rat olfactory system.   Future studies will examine transport of radiolabeled neurotrophins injected into the olfactory epithelium.

Acknowledgements

The author thanks Dr. Kathleen Guthrie for her assistance, guidance, and patience throughout this project. The author also acknowledges Dr. Christine Gall for the opportunity to participate in the research symposium.

Works Cited

1Yuen, Eric C., et al. "Neurotrophins and the neurotrophic factor hypothesis." Neural Notes 1 (1996): 3-7.
2Lipton, Peter, and Ronald Kalil. "Neurotrophic factors-an overview." Promega Notes 50 (1995): 18-22.
3Johnson, Frank, et al. "Neurotrophins suppress apoptosis induced by deafferentation of an avian motor-cortical region." Journal of Neuroscience 17:6 (1997): 2101-11.
4Altar, Anthony C., et al. "Anterograde transport of brain-derived neurotrophic factor and its role in the brain." Nature 389 (1997): 856-60.

 

5Fawcett, James P., et al. "Functional evidence that BDNF is an anterograde neuronal trophic factor in the CNS." Journal of Neuroscience 18:8 (1998): 2808-21.
6von Bartheld, Christopher S., et al. "Anterograde transport of neurotrophins and axodendritic transfer in the developing visual system." Nature 379 (1996): 830-3.
7Conner, James M., et al. "Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport." Journal of Neuroscience 17:7 (1997): 2295-313.
8Brunjes, Peter C., and Lauren L. Frazier. "Maturation and plasticity in the olfactory system of vertebrates." Brain Research Review 11 (1986): 2-27.
9Gong, Qizhi, and Michael T. Shipley. "Evidence that pioneer olfactory axons regulate telencephalon cell cycle kinetics to induce the formation of the olfactory bulb." Neuron 14 (1995): 91-101.
10Guthrie, Kathleen, and Christine M. Gall. "Differential expression of mRNAs for the NGF family of neurotrophic factors in the adult rat central olfactory system." Journal of Comparative Neurology 313 (1991): 95-102.
11Naruse, Ichiro, and Hiromi Keino. "Apoptosis in the developing CNS." Progress in Neurobiology 47 (1995): 135-51.
12Snider, William D., and Jeffrey Lichtman. "Are neurotrophins synaptotrophins?" Molecular and Cellular Neurobiology 47 (1996): 135-55.
13Pinching A. J., and T. P. S. Powell. "Ultrastructural features of transneuronal cell degeneration in the olfactory system." Cell Science 8 (1971): 253-87.
14Najbauer, Joseph, and Michael Leon. "Olfactory experience modulates apoptosis in the developing olfactory bulb." Brain Research 674 (1994): 245-51.
15Thoenen, Hans. "Neurotrophins and neuronal plasticity." Science 270 (1995): 593-8.

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