Jia Cuihong, Hegg Colleen C
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Neurobiol Aging. 2015 Feb;36(2):1045-56. doi: 10.1016/j.neurobiolaging.2014.11.007. Epub 2014 Nov 15.
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.
因衰老而失去嗅觉会损害健康和生活质量。在小鼠嗅觉上皮中，衰老会降低组织稳态和再生能力。同时表达三磷酸肌醇受体3型（IP3R3）和神经增殖因子神经肽Y（NPY）的微绒毛细胞亚型对稳态调节至关重要，但其在衰老过程中的作用尚不清楚。我们推测，IP3R3表达和NPY信号传导与年龄相关的下降是导致与年龄相关的稳态变化和嗅觉功能障碍的原因。我们发现，在24个月的时间里，IP3R3(+)和NPY(+)微绒毛细胞数量、NPY蛋白减少，对NPY介导的增殖的敏感性降低。然而，与野生型相比，在IP3R3基因敲除小鼠中，细胞数量、增殖或嗅觉功能没有进一步的与年龄相关的下降。当损伤由诱导IP3R3介导的NPY释放的satratoxin G引起时，老年IP3R3基因敲除小鼠的增殖反应受损，但由不引起NPY释放的球囊切除术引起的损伤则不会。这些数据确定IP3R3和NPY信号传导是改善嗅觉毒性物质暴露后恢复的靶点。
