Abstract
While the capacity of the olfactory epithelium (OE) to generate sensory neurons continues into middle age in mice, it is presumed that this regenerative potential is present throughout all developmental stages. However, little experimental evidence exists to support the idea that this regenerative capacity remains in late adulthood, and questions about the functionality of neurons born at these late stages remain unanswered. Here, we extend our previous work in the VNO to investigate basal rates of proliferation in the OE, as well as after olfactory bulbectomy (OBX), a commonly used surgical lesion. In addition, we show that the neural stem cell retains its capacity to generate mature olfactory sensory neurons in aged animals. Finally, we demonstrate that regardless of age, a stem cell in the OE, the horizontal basal cell (HBC), exhibits a morphological switch from a flattened, quiescent phenotype to a pyramidal, proliferative phenotype following chemical lesion in aged animals. These findings provide new insights into determining whether an HBC is active or quiescent based on a structural feature as opposed to a biochemical one. More importantly, it suggests that neural stem cells in aged mice are responsive to the same signals triggering proliferation as those observed in young mice.
Highlights
The adult nervous system is limited in its capacity to repair itself
Kondo et al recently found that the rates of proliferation and cell death decline in animals up to 16 months of age (Kondo et al, 2010) but we sought to extend these findings to mice up to 24 months of age given that the expression of odorant receptors may vary significantly throughout the entire lifespan of mice (Rodriguez-Gil et al, 2010; Khan et al, 2013) and the C57BL/6 mouse lifespan ranges up to an extreme of ∼30 months (Konen et al, 1973)
We further the investigation of the dynamics of neurogenesis in the aged olfactory system
Summary
Repositories of neural stem cells are found in the subgranular zone, subventricular zone, and in the neuroepithelium lining the nasal cavity. The mechanisms responsible for widespread aging-induced diminished neurogenesis are unclear. It is possible the function of the stem cell niche surrounding neural stem cells declines with age, or perhaps the regenerative capacity of the stem cell itself is exhausted. The olfactory system is an ideal model system for questions regarding adult neurogenesis, as it is unique in that two of its neuronal populations can be regenerated throughout the life of mammals. One neurogenic population (in the subventricular zone) supplies inhibitory interneurons to the olfactory bulb, while the other (in the nasal neuroepithelium) generates excitatory projection neurons resident in the olfactory epithelium (OE). The basal stem cells that give rise to this latter group in the OE are accessible, studied, and are a rich source
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