Neuroendocrine mechanisms of emotional behavior

描述（由申请人提供）：雌激素的自然波动与人类的许多情感障碍有关。特别是，低水平的循环雌激素与抑郁、焦虑和认知功能障碍的症状增加有关，这些症状通常可以通过激素替代疗法得到改善。关于雌激素影响情绪的机制或作用部位知之甚少，然而，它们可能发生在杏仁核内。因此，需要对杏仁核内雌激素的影响进行全面分析，以进一步了解这种类固醇激素如何影响人类神经精神疾病的发展。目前的建议的目标是（I）确定杏仁核内雌激素的基因组和神经化学作用，以及（II）它们如何影响雌性啮齿动物的恐惧和焦虑。这将通过使用定量实时PCR（Q-PCR）检查杏仁核每个区域内雌激素诱导的基因表达变化来实现。这些实验之后将进行功能研究，其中基因功能敲低与一种新的反义寡核苷酸部分将被用来检查雌激素调节基因如何影响恐惧和焦虑。这些数据将有助于我们了解恐惧和焦虑背后的激素机制。

DESCRIPTION (provided by applicant): Natural fluctuations in estrogens have been associated with a number of affective disorders in humans. In particular, low levels of circulating estrogens are associated with increased symptoms of depression, anxiety and cognitive dysfunction, which can often be ameliorated with hormone replacement therapy. Little is known about the mechanisms or the sites of action through which estrogen is influencing emotion, however, they likely occur within the amygdala. Therefore, a comprehensive analysis of the effects of estrogen within the amygdala is needed to further our understanding of how this steroid hormone influences the development of neuropsychiatric disorders in humans. The goal of the current proposal is to (I) determine the genomic and neurochemical actions of estrogen within the amygdala and (II) how they influence fear and anxiety in female rodents. This will be accomplished by examining estrogen-induced changes in gene expression within each region of the amygdala using quantitative-real-time-PCR (Q-PCR). These experiments will be followed by functional studies in which gene function knockdown with a novel antisense oligonucleotide moiety will be used to examine how estrogen-regulated genes influence fear and anxiety. These data will contribute to our knowledge of the hormonal mechanisms underlying fear and anxiety.