糖皮质激素影响含脑源性神经营养因子的囊泡的树突运输。
Glucocorticoid affects dendritic transport of BDNF-containing vesicles.
作者信息
Adachi Naoki, Numakawa Tadahiro, Nakajima Shingo, Fukuoka Masashi, Odaka Haruki, Katanuma Yusuke, Ooshima Yoshiko, Hohjoh Hirohiko, Kunugi Hiroshi
机构信息
1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Core Research for Evolutional Science and Technology Program (CREST), Japan Science and Technology Agency (JST), Saitama, Japan [3] Department of Biomedical Chemistry, Kwansei Gakuin University, Sanda, Japan.
1] Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan [2] Core Research for Evolutional Science and Technology Program (CREST), Japan Science and Technology Agency (JST), Saitama, Japan [3] Department of Cell Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
出版信息
Sci Rep. 2015 Aug 4;5:12684. doi: 10.1038/srep12684.
Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival, differentiation, and functions in the central nervous system (CNS). Because BDNF protein is sorted into secretory vesicles at the trans-Golgi network in the cell body after translation, transport of BDNF-containing vesicles to the secretion sites is an important process for its function. Here we examined the effect of dexamethasone (DEX), a synthetic glucocorticoid, on BDNF-containing vesicle transport and found that DEX decreased the proportion of stationary vesicles and increased velocity of the microtubule-based vesicle transport in dendrites of cortical neurons. Furthermore, DEX increased huntingtin (Htt) protein levels via glucocorticoid receptor (GR) activation, and reduction in the amount of Htt by a specific shRNA reversed the action of DEX on BDNF vesicle transport. Given that Htt protein is a positive regulator for the microtubule-dependent vesicular transport in neurons, our data suggest that glucocorticoid stimulates BDNF vesicle transport through upregulation of Htt protein levels.
脑源性神经营养因子（BDNF）对于中枢神经系统（CNS）中神经元的存活、分化及功能至关重要。由于BDNF蛋白在细胞体的反式高尔基体网络中翻译后被分选到分泌囊泡中，因此将含BDNF的囊泡运输到分泌位点是其发挥功能的一个重要过程。在此，我们研究了合成糖皮质激素地塞米松（DEX）对含BDNF囊泡运输的影响，发现DEX降低了静止囊泡的比例，并提高了皮质神经元树突中基于微管的囊泡运输速度。此外，DEX通过激活糖皮质激素受体（GR）提高了亨廷顿蛋白（Htt）的水平，而用特异性短发夹RNA减少Htt的量可逆转DEX对BDNF囊泡运输的作用。鉴于Htt蛋白是神经元中微管依赖性囊泡运输的正向调节因子，我们的数据表明糖皮质激素通过上调Htt蛋白水平来刺激BDNF囊泡运输。
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