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Updated: Aug 8, 2026
The Olfactory System as a Model to Study Axonal Growth Patterns and Morphology In Vivo
Published on: October 30, 2014
Cancer treatment and growth cone-associated protein in human olfactory bulb glomeruli
1Center for Alzheimer Disease and Related Disorders, Southern Illinois University School of Medicine, Springfield 62794-1413, USA. bstruble@neuro.siumed.edu
Background:
Growth cone-associated protein (GAP43) is found in growing axons and we hypothesized that systemic treatment with antineoplastic agents should disrupt regeneration of olfactory receptor cells. Disruption of regeneration should be evidenced by decreased presence of growing axons in the olfactory bulb.
Objective:
To evaluate GAP43 in human olfactory bulb in normal controls and in individuals receiving treatment for neoplasms.
Design:
Immunocytochemical studies were performed on autopsied human olfactory bulbs to identify both GAP43 and olfactory marker protein immunoreactivity. The former recognizes growing axons and the latter is a definitive marker of adult olfactory nerve.
Subjects:
Twenty-seven subjects were evaluated. Seven had received either antineoplastic agents and/or x-irradiation of the whole head. Four subjects were young, untreated controls, 10 were age matched to the treated group, and 2 had neoplasms but did not receive antineoplastic agents or irradiation of the head. In addition, 3 subjects with end-stage renal disease were immunostained.
Results:
Subjects treated with antineoplastic agents or x-irradiation of the whole head displayed no statistically significant loss of olfactory bulb glomeruli, but GAP43 immunoreactivity was markedly reduced in all but 1 subject (P<.32). The subjects with end-stage kidney disease showed frank loss of both GAP43 immunoreactivity and olfactory glomeruli.
Conclusions:
Treatment with antineoplastic agents apparently does not damage olfactory epithelium directly but inhibits growth of new axons into the olfactory bulb. This observation suggests that the quality of olfactory experience may change during the course of treatment with antineoplastic agents because the olfactory nerve is not replaced.
Insights
Antineoplastic agents reduce growth-associated protein (GAP43) in the olfactory bulb, indicating inhibited axon regeneration. This suggests potential changes in smell during cancer treatment due to impaired olfactory nerve replacement.
Area of Science:
- Neuroscience
- Oncology
- Regenerative Medicine
Background:
- Growth cone-associated protein (GAP43) is crucial for growing axons.
- Antineoplastic agents may disrupt olfactory receptor cell regeneration.
- This disruption could manifest as reduced axonal growth in the olfactory bulb.
Purpose of the Study:
- To investigate GAP43 presence in human olfactory bulbs.
- To compare GAP43 levels in normal controls versus cancer patients undergoing treatment.
- To assess the impact of antineoplastic agents and radiation on olfactory nerve regeneration.
Main Methods:
- Immunocytochemical analysis of autopsied human olfactory bulbs.
- Detection of GAP43 (recognizes growing axons) and olfactory marker protein (adult olfactory nerve marker).
- Evaluation of 27 subjects, including cancer patients (treated/untreated), controls, and patients with end-stage renal disease.
Main Results:
- No significant loss of olfactory bulb glomeruli in treated subjects.
- Markedly reduced GAP43 immunoreactivity in subjects treated with antineoplastic agents or whole-head irradiation.
- Significant loss of GAP43 and glomeruli in subjects with end-stage renal disease.
Conclusions:
- Antineoplastic agents inhibit new axon growth into the olfactory bulb.
- Olfactory epithelium is likely not directly damaged by these treatments.
- Olfactory nerve regeneration is impaired, potentially altering smell perception during cancer therapy.
