Pro-neurogenesis and anti-dementia properties of tetradecyl 2,3-dihydroxybenzoate through TrkA receptor-mediated signalling pathways.
Pro-neurogenesis and anti-dementia properties of tetradecyl 2,3-dihydroxybenzoate through TrkA receptor-mediated signalling pathways.
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2,3-二羟基苯甲酸十四酯通过 TrkA 受体介导的信号通路促进神经发生和抗痴呆特性。
DOI：
10.1017/s1461145714000558
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Chen, Ling
中科院分区：
文献类型：
--
作者：
Qi, Jianhua;Qi, Jianhua;Chen, Ling;Chen, Ling
据报道，名为ABG001的十四烷基2,3-二羟基苯甲酸酯可促进PC12细胞的神经突生长。在此，我们报告了成年雄性小鼠口服ABG001 5天可以剂量依赖性地增强海马齿状回（DG）新生细胞的存活和神经突生长，而不改变祖细胞的增殖和分化。ABG001给药（0.5 mg/kg）可增强酪氨酸激酶A （TrkA）受体磷酸化，诱导海马ERK、Akt和mTOR磷酸化水平升高。ABG001的前神经发生被TrkA受体抑制剂K252a阻断。相比之下，ERK抑制剂U0126仅减弱abg001增加的新生细胞数量，而PI3K抑制剂LY294002主要阻止abg001增强的神经突生长。Morris水迷宫和Y迷宫测试结果显示，ABG001处理后的小鼠空间认知功能比对照小鼠更优先，且对TrkA受体的阻断敏感。此外，在成年雄性小鼠（a β 25-35-小鼠）中单次注射“聚集”的a β 25-35 （a β 25-35-小鼠）会损害DG中新生细胞的空间记忆、存活和神经突生长，并降低Akt和mTOR的磷酸化。ABG001通过增加TrkA受体诱导的Akt和mTOR的磷酸化，保护新生细胞的存活和神经突生长，并伴有空间认知能力的改善。
Tetradecyl 2,3-dihydroxybenzoate, termed ABG001, has been reported to enhance neurite outgrowth of PC12 cells. Herein, we report that oral administration of ABG001 for five days to adult male mice could dose-dependently enhance survival and neurite growth of newborn cells in hippocampal dentate gyrus (DG) without changes in cell proliferation and differentiation of progenitor cells. The ABG001 administration (0.5 mg/kg) enhanced the phosphorylation of tyrosine kinase A (TrkA) receptor, which induced increases in the levels of ERK, Akt and mTOR phosphorylation in hippocampus. The pro-neurogenesis of ABG001 was blocked by the TrkA receptor inhibitor K252a. By contrast, the ERK inhibitor U0126 attenuated only the ABG001-increased number of newborn cells, while the PI3K inhibitor LY294002 prevented mainly the ABG001-enhanced neurite growth. In comparison with control mice, the mice treated with ABG001 showed a more preferential spatial cognitive function as assessed by Morris water maze and Y maze tests, which was sensitive to the blockade of TrkA receptor. In addition, a single injection (i.c.v.) of 'aggregated' Aβ 25-35 in adult male mice (Aβ 25-35-mice) impaired spatial memory, survival and neurite growth of newborn cells in the DG with reduced phosphorylation of Akt and mTOR. The treatment of Aβ 25-35-mice with ABG001 could protect the survival and neurite growth of newborn cells through increasing TrkA receptor-induced phosphorylation of Akt and mTOR, which was accompanied by the improvement of spatial cognitive performance.
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影响因子：
2.9
作者：
Terry, Alvin V., Jr.;Kutiyanawalla, Ammar;Pillai, Anilkumar
通讯作者：
Pillai, Anilkumar
影响因子：
7.6
作者：
J. R. Stevenson;J. Schroeder;K. Nixon;J. Besheer;F. Crews;C. Hodge
通讯作者：
J. R. Stevenson;J. Schroeder;K. Nixon;J. Besheer;F. Crews;C. Hodge
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7.6
作者：
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影响因子：
5.3
作者：
Rola, R;Raber, J;Fike, JR
通讯作者：
Fike, JR
影响因子：
2.5
作者：
P. Tanapat;N. Hastings;E. Gould
通讯作者：
P. Tanapat;N. Hastings;E. Gould