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说明：原文来自ScienceDaily(2011-4-12)
. F7 g2 h: \) f) j, ~/ v由干细胞之家新闻小组成员laputave翻译（转帖请注明）1 c9 l {; |0 W" o$ S' ]* t& f
' V* ?6 U' v4 I) M0 l1 Z# C翻译正文：
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通过首次利用人类模型进行实验，科学家们发现了抗抑郁药物刺激人体产生新的大脑细胞的机理。这就意味着，研究者们现在可以研发更好更有效的药物来治疗抑郁症。
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之前的研究已经表明，看抑郁药可以刺激产生新的大脑细胞，直到现在这一作用机制仍不为人所知。伦敦国王学院精神病学究院的研究者们发表在《分子精神病学》杂志上的一项研究表明，抗抑郁药物可以调节应激反应中的关键蛋白——糖皮质激素受体（GR），并且，所有看抑郁药都要依赖GR来产生性的大脑细胞。
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预计到2020年，抑郁症将成为全球第二大疾病，最近研究已经表明抑郁症患者表现出一种称作神经新生的大脑机能的减退，也即，新的大脑细胞发育的减少。神经新生机能的减退或许对抑郁症神经衰弱的症状有所贡献，例如情绪低落或记忆障碍。由于运用现今的治疗方式，有近一半的抑郁症患者的症状无法得到改善，因而开发有效的抗抑郁疗法依然有巨大挑战，这使得研究治疗抑郁症的潜在作用机理显得尤为重要。
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国王学院的压力精神病免疫学实验室（SPI-Lab）研究GR在抑郁症中的作用已经有很多年了。这项研究中，科学家们用人类海马干细胞（人类大脑新细胞的来源）建立一个新的模型来探究“在培养皿”[原文in a dish ,不知翻译的对不对]中抗抑郁药对人类大脑细胞的影响。
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身为国王学院的经生病研究院的博士生及该项研究的首席作者的Christoph Anacker说：“首次利用这一在临床上有重大意义的模型进行研究，我们的实验表明抗抑郁药能刺激海马干细胞分裂产生更多干细胞，并且加速这些干细胞分化形成成熟的大脑细胞。此外，我们第一次阐明了压力荷尔蒙具有与看抑郁药相反的作用。通常情况下压力荷尔蒙在抑郁症患者体内含量很高。
# |8 f8 ~: u% Y. e/ x0 ~“我们发现糖皮质激素受体之一细胞上的特殊蛋白，对上述过程是至关重要的。看抑郁药物可以激活GR，GR开启细胞核内某些特定基因，这些基因的产物可以促使未成熟的‘干细胞’转变为成熟的‘脑细胞’。; g& r! T9 G* H' |
“通过增加成年人大脑内新生细胞的数目，看抑郁药物可以抵消压力荷尔蒙对人体造成的伤害，从而可以是抑郁患者克服那些引起情绪低落或记忆障碍的大脑反常现象。”
! D- e j. M3 l7 W; M4 l: @Anacker总结道：“由于已经证实GR在产生新脑细胞中扮演的重要角色，我们现在可以在实验室用神经干细胞建立神经系统疾病模型，用以测试新药和开发更加有效的靶向抗抑郁药物。然而当务之急是未来的研究要探究清楚新生神经的增加对人类行为的所有可能的影响。”
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这项研究由多家机构资助，这些机构分别是位于伦敦南区的英国国家健康研究所心理健康生物医药研究中心，莫兹里英国国民健康保障基金会信托机构，伦敦国王学院，以及英国医学研究委员会。并由几位来自伦敦国王学院精神病学研究中心的资深作者共同主持研究工作，他们分别是SPI实验室心理医学部的卡迈.M.帕里安特博士，行为的细胞学基础研究中心的桑德琳.蒂雷博士和杰克.普莱斯教授。
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注明：个人翻译，理解不准确之处还望各位前辈批评指正 6 ]4 i2 h% P% D0 c# t
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- u. {0 m- e5 z; o原文：
3 q3 b$ x5 G, ]6 RNew Target for Developing Effective Anti-Depressants
& W1 m8 U$ ]8 A0 Z) F. XScienceDaily (Apr. 12, 2011) 9 K% Z& `$ `7 x9 ~% T0 |
For the first time in a human model, scientists have discovered how anti-depressants make new brain cells. This means that researchers can now develop better and more efficient drugs to combat depression.
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Previous studies have shown that anti-depressants make new brain cells, however, until now it was not known how they did it. In a study to be published in the journal Molecular Psychiatry, researchers from the Institute of Psychiatry, King's College London, show that anti-depressants regulate the glucocorticoid receptor (GR) -- a key protein involved in the stress response. Moreover, the study shows that all types of anti-depressant are dependent on the GR to create new cells.
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( u: U5 T2 e0 Y; NDepression is expected to be the second leading burden of disease world wide by the year 2020. Recent studies have demonstrated that depressed patients show a reduction in a process called 'neurogenesis', that is, a reduction in the development of new brain cells. This reduced neurogenesis may contribute to the debilitating psychological symptoms of depression, such as low mood or impaired memory. With as much as half of all depressed patients failing to improve with currently available treatments, developing new effective anti-depressant treatment still remains a great challenge, which makes it crucial to identify new potential mechanisms to target.
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The Laboratory of Stress, Psychiatry and Immunology (SPI-lab) at King's has been looking into the role of the GR in depression for a number of years. In this study, scientists used human hippocampal stem cells, the source of new cells in the human brain, as a new model to investigate 'in a dish' the effects of anti-depressants on brain cells.
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Christoph Anacker, PhD student at the Institute of Psychiatry at King's and lead author of the study said: 'For the first time in a clinically relevant model, we were able to show that anti-depressants produce more stem cells and also accelerate their development into adult brain cells. Additionally, we demonstrate for the first time that stress hormones, which are generally very high in depressed patients, show the opposite effect.+ _8 z* q& n9 H0 r2 Y H: M+ [2 u
'We discovered that a specific protein in the cell, the glucocorticoid receptor, is essential for this to take place. The anti-depressants activate this protein which switches on particular genes that turn immature 'stem' cells into adult 'brain' cells.
9 n& W6 Y+ U5 A'By increasing the number of new-born cells in the adult human brain, anti-depressants counteract the damaging effects of stress hormones and may overcome the brain abnormalities which may cause low mood and impaired memory in depression.'
3 z W7 E: ^4 t, ? c4 {9 n0 BAnacker concludes: 'Having identified the glucocorticoid receptor as a key player in making new brain cells, we will now be able to use this novel stem cell system to model psychiatric illnesses in the laboratory, test new compounds and develop much more effective, targeted anti-depressant drugs. However, first it is important that future studies investigate all possible effects that the increase of neurogenesis has on behaviour in humans.'
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This study was funded by the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust & Institute of Psychiatry, King's College London, and the UK Medical Research Council. The study was jointly led by the senior authors Dr Carmine M. Pariante, at the Laboratory of Stress, Psychiatry and Immunology in the Department of Psychological Medicine, and Dr Sandrine Thuret and Professor Jack Price, at the Centre for the Cellular Basis of Behaviour, all based at Institute of Psychiatry King's College London.+ G! \: A3 _0 X7 D4 Y& P1 M" c
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发表于 2011-4-16 00:14
