期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 17, 期 11, 页码 1847-1861出版社
OXFORD UNIV PRESS
DOI: 10.1017/S1461145714000558
关键词
Hippocampus; nerve growth factor; neurogenesis; tetradecyl 2,3-dihydroxybenzoate; TrkA receptor
资金
- grants 973 [2014CB943303]
- NSFC [81361120247, 31171440]
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 gamma maze tests, which was sensitive to the blockade of TrkA receptor. In addition, a single injection (i.c.v.) of 'aggregated' A beta(25-35) in adult male mice (A beta(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 A beta(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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