Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: lessons from ghrelin knockout mice
Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: lessons from ghrelin knockout mice
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DOI：
10.1507/endocrj.ej14-0436
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发表时间：
2015-03-20
影响因子：
2
通讯作者：
Park, Seungjoon
中科院分区：
文献类型：
--
作者：
Kim, Yumi;Kim, Sehee;Park, Seungjoon
神经发生发生在成年海马体中，并通过饮食限制（DR）而增强，神经发生的增强与循环胃饥饿素水平的增强同时发生。我们之前曾报道过生长素释放肽调节海马体中的成人神经发生。为了研究 ghrelin 在 DR 诱导的成年小鼠海马神经发生中的可能作用，将 ghrelin 敲除 (GKO) 小鼠和野生型 (WT) 小鼠维持 3 个月的 DR 或随意 (AL) 饮食。 DR 增加了 WT 小鼠胃和海马中生长素释放肽的蛋白质水平。施用 BrdU 一天后，维持 AL 饮食的 GKO 小鼠海马齿状回中 BrdU 标记的细胞数量减少。 DR 未能改变 WT 和 GKO 小鼠中祖细胞的增殖。注射 BrdU 4 周后，喂食 AL 的 GKO 小鼠齿状体中的存活细胞数量减少。 DR 增加了 WT 小鼠新生细胞的存活率，但不增加 GKO 小鼠的新生细胞存活率。 WT 和 GKO 小鼠海马中脑源性神经营养因子蛋白的水平相似，并且 WT 和 GKO 小鼠中 DR 均增加了海马中脑源性神经营养因子蛋白的水平。这些结果表明，DR 期间生长素释放肽水平升高可能在增强 DR 诱导的神经发生中发挥重要作用。
Neurogenesis occurs in the adult hippocampus and is enhanced by dietary restriction (DR), and neurogenesis enhancement is paralleled by circulating ghrelin level enhancement. We have previously reported that ghrelin modulates adult neurogenesis in the hippocampus. In order to investigate the possible role of ghrelin in DR-induced hippocampal neurogenesis in adult mice, ghrelin knockout (GKO) mice and wild-type (WT) mice were maintained for 3 months on DR or ad libitum (AL) diets. Protein levels of ghrelin in the stomach and the hippocampus were increased by DR in WT mice. One day after BrdU administration, the number of BrdU-labeled cells in the hippocampal dentate gyrus was decreased in GKO mice maintained on the AL diet. DR failed to alter the proliferation of progenitor cells in both WT and GKO mice. Four weeks after BrdU injection, the number of surviving cells in the dentate gyms was decreased in AL-fed GKO mice. DR increased survival of newborn cells in WT mice, but not in GKO mice. Levels of brain-derived neurotrophic factor protein in the hippocampus were similar between WT and GKO mice, and were increased by DR both in WT and GKO mice. These results suggest that elevated levels of ghrelin during DR may have an important role in the enhancement of neurogenesis induced by DR.