Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2.
Acute stress enhances adult rat hippocampal neurogenesis and activation of newborn neurons via secreted astrocytic FGF2.
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DOI：
10.7554/elife.00362
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发表时间：
2013-04-16
期刊：
影响因子：
7.7
通讯作者：
Kaufer D
中科院分区：
文献类型：
--
作者：
Kirby ED;Muroy SE;Sun WG;Covarrubias D;Leong MJ;Barchas LA;Kaufer D
压力是哺乳动物大脑的一种强有力的调节器。高度保守的应激激素反应影响许多大脑区域，特别是对记忆功能至关重要的海马体。急性应激对成体海马区特有的成体神经干/祖细胞(NPC)群体的影响尚不清楚。我们发现急性应激增加了海马细胞的增殖和星形胶质细胞成纤维细胞生长因子2(FGF2)的表达。急性应激的影响独立于杏仁核基底外侧的神经输入，并通过用皮质酮处理的原代星形胶质细胞的条件培养液处理分离的NPC来模拟。FGF2的中和表明星形胶质细胞分泌的FGF2介导了应激激素诱导的鼻咽癌增殖。急性应激后2周，而不是2天，大鼠也表现出增强的恐惧消退记忆，同时新生神经元的激活增强。我们的发现表明，短暂的压力对海马体有有益的作用，并提高了对大脑适应能力的理解。DOI：http://dx.doi.org/10.7554/eLife.00362.001，一点压力对你有好处。就在100多年前，心理学家罗伯特·耶克斯和约翰·多德森提出，认知能力随着压力的增加而改善，但如果压力水平继续上升，认知能力又会下降。海马体是大脑记忆和情绪调节的关键区域，对主要的应激激素糖皮质激素高度敏感。海马齿状回是海马区的一个特殊区域，含有高密度的糖皮质激素受体，也值得注意的是，它是成年哺乳动物大脑中仅有的两个可以通过一种称为神经发生的过程产生新神经元的区域之一。众所周知，慢性压力会损害记忆，减少神经发生。然而，急性应激的影响并不明确：早期的研究表明，它抑制了新神经元的生成，而最近的几项研究没有观察到任何影响。其他研究表明，急性压力会增加生长因子--刺激细胞生长和增殖的物质--的表达，这似乎表明，压力可能会促进神经发生。现在，Kirby等人。对急性应激对齿状回细胞增殖的影响有了进一步的了解。将大鼠暴露在适度的急性应激源下，即被限制几个小时，会导致背侧而不是腹侧海马区神经发生的增加。注射应激激素皮质酮的大鼠也有同样的效果。在这两种情况下，增强的神经发生伴随着一种名为FGF2的生长因子的表达增加，这种生长因子由被称为星形胶质细胞的胶质细胞产生。有趣的是，Kirby和他的同事发现，在一项记忆测试中，压力过大的老鼠比对照组的老鼠表现得更好。此外，如果老鼠在经历压力的两周后执行任务，就会看到有益的效果，但如果他们在压力后两天执行任务，就不会看到有益的效果。这是有意义的，因为齿状回中的新神经元在生成2周后就能发挥功能，这表明应激诱导的神经发生增加可能是大鼠记忆改善的原因。因此，Kirby和他的同事的工作确定了一种机制，通过这种机制，适度的急性压力可能会对认知产生有益的影响。鉴于急性压力在其他情况下可能是有害的--例如，导致创伤后应激障碍--需要进一步的工作来确定决定对压力的反应是适应性反应还是病理性反应的因素。DOI：http://dx.doi.org/10.7554/eLife.00362.002
Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain. DOI: http://dx.doi.org/10.7554/eLife.00362.001 A little stress can be good for you. Just over 100 years ago, psychologists Robert Yerkes and John Dodson suggested that cognitive performance improves as stress increases, although it falls off again if stress levels continue to rise. The hippocampus is a key brain region for both memory and the regulation of emotion, and is highly sensitive to the main class of stress hormones, glucocorticoids. One particular subregion of the hippocampus, the dentate gyrus, contains a high density of glucocorticoid receptors, and is also notable for being one of only two regions in the adult mammalian brain that can give rise to new neurons via a process called neurogenesis. Chronic stress is known to impair memory and to reduce neurogenesis. However, the effects of acute stress are less clear-cut: early studies suggested that it suppressed the generation of new neurons, whereas several recent studies have observed no effect. Other work has shown that acute stress increases the expression of growth factors—substances that stimulate cellular growth and proliferation—which would seem to suggest that stress could enhance neurogenesis. Now Kirby et al. have obtained further insights into the effects of acute stress on the proliferation of cells in the dentate gyrus. Exposing rats to a moderate acute stressor, namely being restrained for a few hours, led to increased neurogenesis in the dorsal, but not ventral, hippocampus. Injecting rats with the stress hormone corticosterone had the same effect. In both cases, the enhanced neurogenesis was accompanied by increased expression of a growth factor called FGF2, which is produced by glial cells called astrocytes. Intriguingly, Kirby and co-workers found that the stressed rats performed better than control animals in a memory test. Moreover, the beneficial effects were seen if the rats performed the task 2 weeks after their stressful experience, but not if they performed the task 2 days after being stressed. This is pertinent because new neurons in the dentate gyrus become functional 2 weeks after being generated, which suggests that the stress-induced increase in neurogenesis could account for the rats' improved memory. The work of Kirby and co-workers has thus identified a mechanism by which moderate acute stress could have beneficial effects on cognition. Given that acute stress can be harmful in other instances—leading, for example, to post-traumatic stress disorder—further work is required to identify the factors that determine whether a response to stress is adaptive or pathological. DOI: http://dx.doi.org/10.7554/eLife.00362.002