莫里斯水上航行任务
齿状回
神经发生
海马结构
医学
神经干细胞
多发性硬化
水迷宫
芬戈莫德
神经科学
病理
内科学
心理学
生物
干细胞
免疫学
细胞生物学
作者
A. Stessin,Matei Banu,Mariano Guardia Clausi,Nicholas A. Berry,John A. Boockvar,Samuel Ryu
标识
DOI:10.1016/j.neulet.2017.08.025
摘要
This study evaluates FTY720/Fingolimod, modulator of sphingosine-1-phosphate (S1P) receptor, as a potential mitigator of radiation-induced neurocognitive dysfunction. To study radiation-induced neurocognitive deficits, 6 week-old C57/Bl/6J mice received 0 or 7 Gy cranial irradiation and were treated with FTY720 or vehicle for seven weeks. Fear conditioning and Morris water maze were then employed to test learning and memory. Immunohistochemical staining for neural progenitor cells (NPCs) and mature neurons was used to assess changes in hippocampal neurogenesis. To test effects on tumor growth, mice harboring brain tumor xenografts were treated with FTY720 or vehicle for six weeks. In irradiated mice, learning deficits were manifested by significantly longer latency times in the Morris Water Maze compared to non-irradiated controls (p = 0.001). The deficits were fully restored by FTY720. In irradiated brains, FTY720 maintained the cytoarchitecture of the dentate gyrus granular cell layer and partially restored the pool of NPC. In mice harboring brain tumor stem cell (BTSC) xenografts FTY720 delayed tumor growth and improved survival (p = 0.012). FTY720 mitigates radiation-induced learning dysfunction. A partial restoration of neurogenesis was observed. Furthermore, FTY720 appears to delay tumor growth and improve survival in a xenograft glioma mouse model.
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