Influence of Androgens on the Amygdala

描述（由申请人提供）：这一系列研究的目的是了解大脑中的性别差异是如何产生的，以及这些性别差异的神经解剖学性质。 公共卫生受到许多精神疾病的影响，这些疾病在一种性别中出现的频率高于另一种性别，这表明神经解剖学上的性别差异使一种性别更容易受到特定异常的影响，而不太容易受到其他异常的影响。 杏仁核在活动和解剖学上表现出性别差异，并与精神分裂症、自闭症、焦虑症、抑郁症和双相情感障碍等几种性别偏见的公共卫生问题密切相关。 内侧后背杏仁核（MePD）似乎对性激素特别敏感，并挑战了公认的神经性别差异是雌激素依赖性的理论。 在MePD雄激素受体（AR）是必要的完全形成的性别差异在几个方面的神经解剖，包括区域体积，神经元索马大小，和神经元数量。 然而，MePD细胞解剖学的其他方面也可能导致杏仁核的性别差异。 在其他性二态脑区，星形胶质细胞与当地的GABA神经元相互作用，产生细胞形态的变化。 这种相互作用是由性激素介导的，在MePD中可能存在类似的关系。 我们最近已经确定了戏剧性的性别和半球的差异星形胶质细胞的数量和形态的MePD的一部分，以前的建议。 基于这一发现，本研究将1）利用免疫细胞化学和体视学来计数和追踪MePD内含有GABA的神经元的索马体，寻找GABA神经元数量或大小的性别差异3）评估成年雄激素操作对星形胶质细胞和GABA神经元的影响和4）利用荧光标记和共聚焦显微镜来鉴定哪些细胞类型含有AR，从而确定雄激素在MePD中的作用位置。 2. 对精神障碍患病率的粗略检查揭示了许多病理学中强烈的性别偏见，表明大脑功能的性别差异。 通过探索男性和女性大脑的不同以及这些差异是如何产生的，我们可能能够为此类疾病开发更有针对性和有效的治疗方法。 这项研究的重点是大脑中对性激素高度敏感并与多种性别偏见疾病密切相关的区域，即杏仁核。 这项研究还针对特定的细胞类型，以确定性激素在哪里改变杏仁核神经解剖结构。

DESCRIPTION (provided by applicant): The objective of this line of research is to understand how sex differences in the brain arise and the neuroanatomical nature of these sex differences. Public health is affected by numerous mental diseases which appear more frequently in one sex than the other, suggesting sex differences in neural anatomy make one sex more susceptible to particular abnormalities and less susceptible to others. The amygdala demonstrates sex differences in activity and anatomy and is closely linked to several sex-biased public health concerns such as schizophrenia, autism, anxiety, depression, and bi-polar disorder. The medial postero-dorsal amygdala (MePD) appears especially sensitive to sex hormones and challenges the accepted theory that neural sex differences are estrogen-dependent. In the MePD androgen receptors (AR) are necessary for complete formation of sex differences in several aspects of neural anatomy including regional volume, neuronal soma size, and neuron number. However, other aspects of MePD cellular anatomy may also contribute to sex differences in the amygdala. In other sexually dimorphic brain regions, astrocytes interact with local GABA neurons to produce changes in cell morphology. This interaction is mediated by sex hormones and it is likely that a similar relationship may exist in the MePD. We have recently identified dramatic sex and hemisphere differences in astrocyte number and morphology in the MePD as part of a prior proposal. Building upon that discovery, this research will 1) utilize immunocytochemistry and stereology to count and trace the soma of GABA containing neurons within the MePD, looking for sex difference in GABA neuron number or size 3) assess the influence of adult androgen manipulations on astrocytes and GABA neurons and 4) utilize fluorescent labeling and confocal microscopy to identify which cell types contain AR, thus determining where androgens are acting in the MePD. 2. A cursory examination of mental disorder prevalences reveals strong sex-biases in numerous pathologies, suggesting sex-differences in how the brain functions. By exploring how male and female brains are different and how these differences arise, we may be able to develop more targeted and effective treatments for such diseases. This research focuses on a region of the brain that is both highly sensitive to sex hormones and closely linked to a multitude of sex-biased diseases, the amygdala. This research also targets specific cell types in order to identify where sex hormones are acting to alter amygdala neural anatomy.