Dynamics of neural stem cells in the adult mammalian brain under stress conditions.

应激条件下成年哺乳动物大脑中神经干细胞的动态。

• 批准号: 16500251
• 负责人: HITOSHI Seiji
• 金额: $ 2.37万
• 依托单位: National Institute for Physiological Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16500251/
• 关键词: Stress; Forced swimming; Maternal separation; Adult neurogenesis; Subventricular zone; Hippocampus; Neural stem cell; Neurosphere assay; Neuroshere assay; Neuroshpere assay

Adult neurogenesis, which occurs in the olfactory bulb and dentate gyrus (DG) of the hippocampus in rodents, may play significant roles in brain function. Cell proliferation in the DG is reduced after exposure to psychosocial stress, yet the molecular and cellular mechanisms underlying this reduction remain to be elucidated. In the present study, we utilize the forced swim model of stress in the mouse to determine the effects of chronic stress on neural stem cells (NSCs) in the subventricular zone (SVZ). Chronic stress decreased the number of NSCs in the SVZ, the decrease persisted for weeks after the cessation of stress, but was reversed by treatment with antidepressant drugs. The effects of chronic stress on NSCs are blocked by bilateral adrenalectomy in vivo, and corticosterone attenuates neurosphere formation by adult NSCs in vitro. In contrast, serotonin increased survival of the NSCs when exposure was in vitro and expanded the size of NSC pool in the SVZ when serotonin was infused to the lateral ventricle in vivo. These results suggest that the number of NSCs under chronic stress conditions are regulated by the balance between the action of glucocorticoids and serotonin and provide an insight to the molecular mechanisms underlying pharmacological action of antidepressant drugs.

成体神经发生发生在啮齿类动物的嗅球和海马齿状回(DG)，可能在脑功能中发挥重要作用。在暴露于心理社会应激后，DG中的细胞增殖减少，但这种减少的分子和细胞机制仍有待阐明。在本研究中，我们利用小鼠强迫游泳应激模型来确定慢性应激对脑室下区神经干细胞(NSCs)的影响。慢性应激使SVZ内NSCs数量减少，应激停止后这种减少持续数周，但经抗抑郁药物治疗后被逆转。体内双侧肾上腺切除可阻断慢性应激对神经干细胞的影响，体外皮质酮可抑制成年神经干细胞神经球的形成。相反，在体外暴露时，5-羟色胺可增加神经干细胞的存活率，并在体内将5-羟色胺注入侧脑室时，扩大了SVZ内NSC池的大小。这些结果表明，慢性应激条件下神经干细胞的数量受糖皮质激素和5-羟色胺之间的平衡调节，为抗抑郁药物药理作用的分子机制提供了新的线索。

项目成果

An N-glycans structure correlates with pulmonary metastatic ability of cancer cells.

N-聚糖结构与癌细胞的肺转移能力相关。

• 发表时间: 2006
• 期刊: Biochemistry Biophysics Research Communication 340
• 作者: Sakuma K;Fujimoto I;Hitoshi S;Tanaka F;Ikeda T;Tanabe K;Toyokuni S;Wada H;Mio T;Mishima M;Ikenaka K
• 通讯作者: Ikenaka K

Notch signaling is required to maintain all neural stem cell populations - Irrespective of spatial or temporal niche

• DOI: 10.1159/000090751
• 发表时间: 2006-01-01
• 期刊: DEVELOPMENTAL NEUROSCIENCE
• 影响因子: 2.9
• 作者: Alexson, TO;Hitoshi, S;van der Kooy, D
• 通讯作者: van der Kooy, D

Primitive neural stem cells from the mammalian epiblast differentiate to definitive neural stem cells under the control of Notch signaling

• DOI: 10.1101/gad.1208404
• 发表时间: 2004-08-01
• 期刊: GENES & DEVELOPMENT
• 影响因子: 10.5
• 作者: Hitoshi, S;Seaberg, RM;van der Kooy, D
• 通讯作者: van der Kooy, D