CNS Estrogen Receptors and Social Behavior

中枢神经系统雌激素受体和社会行为

• 批准号: 6768849
• 负责人: Bruce S Cushing
• 金额: $ 15.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6768849
• 关键词: aggression; behavioral /social science research tag; brain mapping; estrogen receptors; estrogens; ethology; model design /development; neuropsychology; parent offspring interaction; protein localization; receptor expression; sex behavior; social behavior; social model; transfection; vole

DESCRIPTION (provided by applicant): Recombinant adeno-associated viral (rAAV) vectors can be used to directly introduce genes into cells making local manipulation of receptors possible and site-specifically alter the sensitivity of an animal to hormones. The goal of this study is to use this developing technology to enhance ERalpha in male prairie voles (Microtus ochrogaster). E influences a variety of male and female behaviors, including aggression, affiliation, social preferences, parental behavior, and mating. Prairie voles provide a unique opportunity to use rAAV to understand the role of steroids in regulating social behavior. Foremost, prairie voles are highly social and monogamous, displaying many social interactions similar to humans, making them a better rodent model for studying social behavior than species such as rats and mice. The development of ER knockout (KO) mice (a and a) has provided significant insight into the actions of E and with the advent of rAAV ER can be replaced in specific areas providing a powerful tool for examining the effects of E. A disadvantage of ERKO mice is they not only lack ER as adults, but also are not exposed to the organizational effects of E during development. In contrast prairie voles are subject to the developmental effects of E, but at the same time, males, at least from Illinois, express little or no ERalpha, and significantly less than females, in the BST and the MeA. In rats and mice, where male/female social interactions are often limited to mating, both males and females express high levels of ERalpha in the MeA and BST. The MeA and BST play a major role in regulating social behavior, and a comparison of the pattern found in prairie voles with rats and mice suggests that the lack of ERalpha in these areas could account for increased social behavior displayed by male prairie voles. This possibility is further supported by comparing social behavior and ERalpha between prairie voles from Illinois (IL), which are monogamous, and Kansas (KN), which are less social and show many polygynous characteristics. KN males display an ERalpha pattern intermediate to IL prairie voles and rats, with KN males expressing significantly more ERalpha in the BST and the MA than IL males, but less than KN females in the BST. IL male prairie voles will be transfected with rAAV-ERalpha in the BST and MeA and transfected, sham and control males will be tested for aggression, parental behavior, partner preference, social contact (same and opposite sex), and sexual behavior, with the prediction being that increasing ERalpha will decrease affiliation and increase aggression.

描述（由申请人提供）：重组腺相关病毒（RAAV）载体可用于将基因直接引入细胞中，从而使局部对受体的操纵成为可能，并特异性地改变了动物对激素的敏感性。这项研究的目的是利用这项开发的技术来增强雄性草原田鼠（Microtus ochrogaster）的埃拉法。 E影响各种男性和女性行为，包括侵略，隶属关系，社会偏好，父母的行为和交配。草原田鼠提供了一个独特的机会，可以利用Raav了解类固醇在调节社会行为中的作用。最重要的是，草原田鼠是高度社交和一夫一妻制的，表现出许多与人类类似的社交互动，使它们成为研究社会行为的啮齿动物模型，而不是大鼠和小鼠等物种。 ER敲除（KO）小鼠（A和A）的开发提供了对E的作用的重大见解，并且可以在特定区域取代Raav Er的出现，从而提供了一个有力的工具来检查E Erko小鼠的损失，它们不仅是成年人缺乏ER，而且还没有向E期间E的组织效应。相比之下，草原田鼠受到E的发育效果，但与此同时，男性，至少来自伊利诺伊州，几乎没有或没有Eralpha，并且在BST和MEA中的男性明显小于女性。在男性/女性社交互动通常仅限于交配的大鼠和小鼠中，男性和女性在MEA和BST中表现出高水平的Eralpha。 MEA和BST在调节社会行为方面起着重要作用，对草原田鼠与大鼠和小鼠的模式的比较表明，在这些领域缺乏Eralpha可能会导致男性草原田径展示的社会行为增加。通过比较来自伊利诺伊州（IL）的大草原田鼠之间的社会行为和埃拉帕（Eralpha），这是一夫一妻制的，而堪萨斯州（kn）的社会行为和埃拉帕（Eralpha），这些田鼠和堪萨斯州（KN）的社会较少，并且表现出许多一夫多妻的特征。 kN男性显示出eralpha模式中间与Il Prairie田鼠和大鼠相比，BST和MA中的Eralpha的表现明显高于IL男性，但BST中的kn雌性小于kn雌性。 IL男性草原田鼠将在BST和MEA中用Raav-Arerpha转染，并转染，假男性和对照雄性将接受侵略性，父母行为，伴侣的偏好，社交接触（相同的和异性）以及性行为以及性行为的测试，并且预测会增加ERALPHA会降低隶属关系和增加攻击性。