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Age-related changes of the regeneration mode in the mouse peripheral olfactory system following olfactotoxic drug
Keigo Suzukawa1, Kenji Kondo, Kaori Kanaya
1Department of Otolaryngology-Head and Neck Surgery, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan. suzukawa-tky@umin.ac.jp
Abstract:
We investigated age-related changes in the mode of regeneration in the mouse peripheral olfactory system after olfactotoxic drug-induced damage. Mice at postnatal ages of 10 days, 3 months, and 16 months were given an intraperitoneal injection of methimazole to produce damage in the olfactory neuroepithelium. The olfactory neuroepithelia were harvested and analyzed immunohistochemically at various postlesion timepoints, from 1 day through to 94 days, to investigate neuroepithelial cell proliferation, the time course of neuronal differentiation, the reconstitution of neuroepithelium, and the innervation of the olfactory bulb. Functional recovery was assessed using the vanillin avoidance behavioral test. The chronological pattern in the expression of Ki67, beta III tubulin, and olfactory marker protein, molecular markers for neuronal cell proliferation and differentiation, changed similarly among the different age groups. In contrast, the extent of neuroepithelial cell proliferation after injury decreased with age, and the final histological recovery of the olfactory neuroepithelium and the innervation of the olfactory bulb were significantly smaller in the 16-month-old group compared to the younger age groups. These results suggest that the age-related decline in the capacity of olfactory neuroepithelium to reconstitute neuroepithelium is associated with its age-related decrease in proliferative activity after the neuroepithelial injury rather than changes in the process of neuronal differentiation. In spite of these incomplete anatomical recoveries, 16-month-old mice regained the ability to avoid vanillin solution by 1 month postlesion, suggesting that the extent of anatomical epithelial damage is not necessarily proportional to the threshold of olfactory perception.
Insights
Aging mice show reduced olfactory neuroepithelium regeneration due to decreased cell proliferation, not impaired neuronal differentiation. Despite anatomical deficits, older mice regain olfactory function.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Aging Research
Background:
- The olfactory system's ability to regenerate declines with age.
- Understanding age-related regenerative capacity is crucial for treating olfactory dysfunction.
Purpose of the Study:
- To investigate age-related changes in olfactory neuroepithelium regeneration after chemical injury.
- To determine if reduced regeneration in aging mice is due to impaired cell proliferation or neuronal differentiation.
Main Methods:
- Mice of different ages (10 days, 3 months, 16 months) received methimazole to induce olfactory neuroepithelium damage.
- Immunohistochemistry was used to assess cell proliferation (Ki67), neuronal differentiation (beta III tubulin, OMP), and tissue reconstitution.
- Olfactory function was evaluated using a vanillin avoidance behavioral test.
Main Results:
- Cell proliferation and differentiation marker expression followed similar timelines across age groups.
- Older mice (16 months) exhibited significantly reduced neuroepithelial cell proliferation and incomplete histological recovery.
- Despite reduced anatomical repair, older mice recovered olfactory-guided behavior.
Conclusions:
- Age-related decline in olfactory neuroepithelium regeneration is primarily linked to decreased proliferative activity post-injury.
- Neuronal differentiation processes remain largely unaffected by age in this model.
- Olfactory functional recovery may not be directly proportional to the extent of anatomical regeneration.
