Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa
Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa
复制标题
热量限制会减少小鼠嗅粘膜嗅毒性粘膜损伤后基底细胞增殖并导致神经上皮再生恶化
DOI：
10.1007/s00441-019-03047-1
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发表时间：
2019
影响因子：
3.6
通讯作者：
Yamasoba Tatsuya
中科院分区：
文献类型：
--
作者：
Iwamura Hitoshi;Kondo Kenji;Kikuta Shu;Nishijima Hironobu;Kagoya Ryoji;Suzukawa Keigo;Ando Mizuo;Fujimoto Chisato;Toma-Hirano Makiko;Yamasoba Tatsuya
评价热量限制（CR）对小鼠嗅神经上皮细胞动力学和基因表达的影响。8周龄雄性C57 BL/6小鼠喂食对照颗粒（104 kcal/周）或CR颗粒（67 kcal/周）。嗅觉神经上皮细胞的细胞结构在未受伤的条件下，其损伤后的嗅觉毒性化学物质，甲巯咪唑，进行了比较与控制和CR饮食喂养的小鼠。在未损伤条件下，CR组3个月时嗅觉标记蛋白（OMP）阳性嗅觉受体神经元和Ki 67阳性增殖基底细胞明显少于对照组。在对照组和CR组中，他巴唑诱导的粘膜损伤后Ki 67阳性基底细胞的数量增加，但CR组的增加不太稳健。CR组在他巴唑给药后2个月神经上皮的恢复不如对照组完全。这些组织学变化具有区域特异性。OMP阳性神经元的减少在嗅粘膜的前部区域是突出的。使用DNA微阵列和定量实时聚合酶链反应的基因表达分析表明，两个炎性细胞因子，白细胞介素-6和趋化因子配体1的表达水平升高，在嗅粘膜的CR组与对照组相比。这些结果表明，CR可能不利于维持嗅神经上皮，特别是当它受损。
The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured.