Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation.
Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation.
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DOI：
10.1016/j.neurobiolaging.2014.11.007
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发表时间：
2015-02
影响因子：
4.2
通讯作者：
Hegg CC
中科院分区：
文献类型：
--
作者：
Jia C;Hegg CC
由于衰老而丧失嗅觉会损害健康和生活质量。在小鼠嗅觉上皮(OE)中，衰老降低了组织的动态平衡和再生能力。微绒毛细胞亚型同时表达三磷酸肌醇受体3(IP3R3)和神经增殖因子神经肽Y(NPY)，对调节体内平衡至关重要，但其在衰老中的作用尚不明确。我们假设，与年龄相关的IP3R3表达和NPY信号的下降是与年龄相关的稳态变化和嗅觉功能障碍的基础。我们发现，在24个月内，IP3R3+和NPY+微绒毛细胞数量和NPY蛋白减少，对NPY介导的增殖的敏感性降低。然而，在IP3R3缺陷小鼠中，与野生型相比，没有进一步的与年龄相关的细胞数量、增殖或嗅觉功能的减少。在老年IP3R3基因缺陷小鼠中，当损伤是由沙曲霉毒素-G引起时，增殖反应受到损害，这种损伤诱导IP3R3介导的NPY释放，而不是通过球部切除，不引起NPY释放。这些数据表明，IP3R3和NPY信号通路是嗅觉毒物暴露后改善恢复的靶点。
Losing the sense of smell due to aging compromises health and quality of life. In the mouse olfactory epithelium (OE) 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 to 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.
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影响因子：
3.3
作者：
Jia, C.;Doherty, J. P.;Crudgington, S.;Hegg, C. C.
通讯作者：
Hegg, C. C.
影响因子：
3.5
作者：
Jia, Cuihong;Hegg, Colleen Cosgrove
通讯作者：
Hegg, Colleen Cosgrove
影响因子：
3.7
作者：
Jia C;Hayoz S;Hutch CR;Iqbal TR;Pooley AE;Hegg CC
通讯作者：
Hegg CC
影响因子：
5.3
作者：
Enwere, E;Shingo, T;Weiss, S
通讯作者：
Weiss, S
影响因子：
64.8
作者：
Hansel, DE;Eipper, BA;Ronnett, GV
通讯作者：
Ronnett, GV