Steroid Receptors and Brain Sex Differences

类固醇受体和大脑性别差异

基本信息

批准号：
7432633
负责人：
ANTHONY P AUGER
金额：
$ 30.14万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7432633
关键词：
Acute Adult Alzheimer&apos s Disease Asperger Syndrome Attention Autistic Disorder Behavior Behavioral Biological Assay Brain Cells Child Cultured Cells Data Development Disease Dopamine Dopamine Receptor Dyslexia Estrogen Receptors Exhibits Female Human Hyperactive behavior Life Ligand Binding Ligand Binding Domain Ligands Localized Mediating Mental Depression Mental disorders Mothers Multiple Sclerosis Neurologic Neurons Ovarian Steroid Hormone Physiological Play Process Receptor Cell Reproduction Research Personnel Rodent Rodent Model Role Sex Behavior Sex Characteristics Social Behavior Social Development Steroid Receptors Steroids Syndrome Testing Woman brain morphology day design dopamine D5 receptor male men programs receptor research study response social social organization steroid hormone steroid hormone receptor transmission process

项目摘要

DESCRIPTION (provided by applicant): During early brain development, steroid hormone exposure differentiates male from female brain. Although there are numerous physiological and behavioral differences between men and women, perhaps the most profound sex differences are in neurological and psychiatric disorders. For example, women are more likely to exhibit signs of depression, multiple sclerosis, and Alzheimer's disease. Men are more likely to exhibit signs of attention-deficit hyperactivity, autism, and dyslexia. As most sex differences in the brain are a result of early steroid hormone exposure, it is possible that sex differences in some disorders are partly influenced by abnormal steroid receptor action in developing brain. Therefore it is important to understand how steroid receptor activity is regulated in developing brain. Previously, it was assumed that steroid receptors were only activated by steroid hormones; however, recent data indicate that steroid receptors are also activated in the absence of steroid, referred to as ligand-independent activation. Although numerous investigators are currently studying ligand-independent activation of steroid receptors in cell culture assays and in adult female brain, few studies investigate the role of ligand-independent activation of steroid receptors in brain development. We plan to investigate the functional role ligand-independent activation of estrogen receptors (ER) in developing brain. Our recent data indicate that acute changes in dopamine transmission during the first few days of life can dramatically alter the developmental organization of social play behavior by activating ER in a ligand-independent manner. We believe that these data are not only exciting in that they suggest a potential steroid hormone independent mechanism for sexual differentiation of the brain, but they also investigate the developmental organization of social play behavior. As social play behavior is dramatically disrupted in children with Autism and Asperger's syndrome, and social play behavior in rodents has been used as a rodent model for the study of autism, it is possible that these data will further our understanding of how sexually dimorphic social disorders occur during brain development.

描述（由申请人提供）：在早期大脑发育期间，类固醇激素暴露与雌性大脑区分开。尽管男女之间存在许多生理和行为差异，但最深刻的性别差异可能是神经和精神疾病。例如，女性更有可能表现出抑郁症，多发性硬化症和阿尔茨海默氏病的迹象。男性更有可能表现出注意力缺陷多动，自闭症和阅读障碍的迹象。由于大脑中的大多数性别差异是早期类固醇激素暴露的结果，因此某些疾病中的性别差异可能部分受到发育中大脑异常的类固醇受体作用的影响。因此，重要的是要了解如何在发育中的大脑中调节类固醇受体活性。以前，假定类固醇受体仅被类固醇激素激活。但是，最近的数据表明，在没有类固醇的情况下，类固醇受体也被激活，被称为配体无关的激活。尽管许多研究者目前正在研究类固醇受体在细胞培养测定和成年雌性大脑中的非配体非依赖性激活，但很少有研究研究类固醇受体在脑发育中非配体非依赖性激活的作用。我们计划研究雌激素受体（ER）在发育中的大脑中的功能性作用。我们最近的数据表明，在生命的头几天，多巴胺传播的急性变化可以通过以不依赖配体的方式激活ER来极大地改变社会游戏行为的发展组织。我们认为，这些数据不仅令人兴奋，因为它们暗示了潜在的类固醇激素独立的大脑性别分化机制，而且还研究了社会游戏行为的发展组织。由于自闭症和阿斯伯格综合症儿童的社交行为受到了极大的破坏，啮齿动物的社交行为被用作自闭症研究的啮齿动物模型，因此这些数据可能会进一步了解我们对性二态社交障碍的理解发生在大脑发育过程中。