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Published on: July 24, 2019
Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation
1Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Abstract:
Losing the sense of smell because of aging compromises health and quality of life. In the mouse olfactory epithelium, aging reduces the capacity for tissue homeostasis and regeneration. The microvillous cell subtype that expresses both inositol trisphosphate receptor type 3 (IP3R3) and the neuroproliferative factor neuropeptide Y (NPY) is critical for regulation of homeostasis, yet its role in aging is undefined. We hypothesized that an age-related decline in IP3R3 expression and NPY signaling underlie age-related homeostatic changes and olfactory dysfunction. We found a decrease in IP3R3(+) and NPY(+) microvillous cell numbers and NPY protein and a reduced sensitivity to NPY-mediated proliferation over 24 months. However, in IP3R3-deficient mice, there was no further age-related reduction in cell numbers, proliferation, or olfactory function compared with wild type. The proliferative response was impaired in aged IP3R3-deficient mice when injury was caused by satratoxin G, which induces IP3R3-mediated NPY release, but not by bulbectomy, which does not evoke NPY release. These data identify IP3R3 and NPY signaling as targets for improving recovery following olfactotoxicant exposure.
Insights
Aging impairs smell by reducing microvillous cell numbers and neuropeptide Y (NPY) signaling. Inositol trisphosphate receptor type 3 (IP3R3) deficiency prevented age-related decline, suggesting IP3R3 and NPY are key targets for olfactory recovery.
Area of Science:
- Neuroscience
- Aging Research
- Olfactory Biology
Background:
- Aging compromises health and quality of life by reducing the sense of smell.
- The mouse olfactory epithelium's capacity for tissue homeostasis and regeneration declines with age.
- Microvillous cells expressing inositol trisphosphate receptor type 3 (IP3R3) and neuropeptide Y (NPY) are crucial for homeostasis, but their role in aging is unknown.
Purpose of the Study:
- To investigate the hypothesis that age-related decline in IP3R3 expression and NPY signaling contribute to olfactory dysfunction.
- To determine the role of IP3R3 and NPY signaling in age-related changes in olfactory homeostasis and regeneration.
Main Methods:
- Comparison of olfactory epithelium in aged (24 months) wild-type and IP3R3-deficient mice.
- Assessment of microvillous cell numbers, NPY protein levels, and NPY-mediated proliferation.
- Evaluation of olfactory function and proliferative responses following satratoxin G or bulbectomy injury.
Main Results:
- Aged mice showed decreased IP3R3(+) and NPY(+) microvillous cells, reduced NPY protein, and impaired NPY-mediated proliferation.
- IP3R3-deficient mice did not exhibit further age-related decline in cell numbers, proliferation, or olfactory function compared to wild-type controls.
- The proliferative response to satratoxin G was impaired in aged IP3R3-deficient mice, but not to bulbectomy.
Conclusions:
- Age-related olfactory dysfunction is linked to reduced IP3R3 and NPY signaling in microvillous cells.
- IP3R3 plays a critical role in mediating NPY-induced proliferation and olfactory recovery after specific injuries.
- Targeting IP3R3 and NPY signaling presents a potential therapeutic strategy for improving olfactory recovery after exposure to olfactotoxicants.
