SGER: Gene Arrays as a Tool to Explore Brain Stress Mechanisms

从细菌到人类的所有生物体似乎都有一套内置程序，这些程序对于应对环境中偏离最佳状态的情况至关重要。 为了做到这一点，他们依赖于检测这些变化的机制，以及应对机制;这些机制共同构成了压力系统。 这项建议的重点是压力系统的一个关键组成部分，边缘-下丘脑-垂体-肾上腺（LHPA）轴，以及大脑中哪些基因受到这个“压力系统”的影响。 LHPA通过称为糖皮质激素的应激激素来影响其影响。 糖皮质激素释放到血液中，并冲击许多靶点。 大脑是许多靶点之一;糖皮质激素通过直接作用于细胞表面（神经元机制），以电的方式打开或关闭脑细胞。 此外，糖皮质激素可以作用于神经元细胞内的遗传密码，以影响细胞产生的因子，这些因子可以对附近或远处的细胞产生长期影响（基因组机制）。 由于糖皮质激素通过神经元和基因组机制的结合发挥作用，它们的作用可以在几分钟内感受到，但也可以在压力事件结束后持续很长时间。 持续较长时间的影响可能是有害的（即记忆丧失，细胞死亡）。 本申请提出研究慢性应激激活的基因，并鉴定哪些基因与糖皮质激素的作用直接相关。 我们使用一种名为基因阵列的新技术，它允许我们同时筛选不同大脑区域中的数千个已知和未知基因。 我们将利用这笔资金提高这项技术的灵敏度，以检测大脑中的多个基因。 我们希望通过提供对大脑中压力影响的理解，并通过提供对神经科学领域有价值的技术工具的改进做出贡献。

All living organisms from bacteria to human, appear to have a set of built-in-programs critical for coping with deviations from the optimum in their environment. To do so, they rely on mechanisms for detecting these changes, as well as mechanisms for coping; together, these mechanisms constitute the stress system. This proposal focuses on a key component of the stress system, the limbic-hypothalamo-pituitary-adrenal (LHPA) axis, and what genes are influenced in brain by this 'stress system'. The LHPA effects its influence via stress hormones called glucocorticoid. Glucocorticoids are released into blood, and impinge on numerous targets. The brain is one of the many targets; here glucocorticoids turns brain cells "on or off" electrically by acting directly on the surface of the cells (neuronal mechanisms). In addition, glucocorticoids can act on the genetic code within the neuronal cell to influence factors made by the cell that can have long lasting effects on cells close by, or far away (genomic mechanisms). Because glucocorticoids work through a combination of neuronal and genomic mechanisms, their effects can be felt within minutes, but can also last long after the stressful event has terminated. The effects that last longer for longer time can be detrimental (i.e. loss of memory, cell death). This application proposes to study the genes activated by chronic stress and identify which are directly related to glucocorticoid action. We use a novel technique called Gene Array that allows us to simultaneously screen thousands of genes, both known and unknown, within different brain areas. We shall use the funding to improve the sensitivity of this technique to detect multiple genes in brain. We hope by providing the understanding of the effects of stress in the brain and contribute by providing the refinement of a technical tool that will be valuable to the field of neuroscience.