CNS Estrogen Receptors and Social Behavior

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导入细胞，使受体的局部操作成为可能，并位点特异性地改变动物对激素的敏感性。本研究的目的是利用这项正在开发的技术，以提高ER α在雄性草原田鼠（Microtus ochrogaster）。E影响各种各样的男性和女性行为，包括攻击性，从属关系，社会偏好，父母行为和交配。草原田鼠提供了一个独特的机会，使用rAAV了解类固醇在调节社会行为的作用。最重要的是，草原田鼠是高度社会化和一夫一妻制的，表现出许多类似于人类的社会互动，使它们成为比大鼠和小鼠等物种更好的研究社会行为的啮齿动物模型。ER敲除（KO）小鼠（a和a）的开发已经提供了对E的作用的重要见解，并且随着rAAV的出现，ER可以在特定区域被取代，从而为检查E的作用提供了有力的工具。ERKO小鼠的一个缺点是它们不仅缺乏成年ER，而且在发育过程中也没有暴露于E的组织效应。相比之下，草原田鼠是受E的发展影响，但在同一时间，男性，至少从伊利诺伊州，表达很少或没有ER α，并显着低于女性，在BST和MeA。在大鼠和小鼠中，雄性/雌性的社会互动通常仅限于交配，雄性和雌性在MeA和BST中表达高水平的ER α。MeA和BST在调节社会行为中起着重要作用，草原田鼠与大鼠和小鼠的模式比较表明，这些区域缺乏ER α可以解释雄性草原田鼠表现出的社会行为增加。这种可能性得到了进一步的支持，比较社会行为和ER α之间的草原田鼠从伊利诺伊州（IL），这是一夫一妻制，和堪萨斯（KN），这是社会性较低，并显示出许多一夫多妻制的特点。KN男性显示ER α模式中间IL草原田鼠和大鼠，KN男性表达显着更多的ER α在BST和MA比IL男性，但低于KN女性在BST。IL雄性草原田鼠将在BST和MeA中用rAAV-ER α转染，并且将测试转染的、假手术和对照雄性的攻击性、亲代行为、伴侣偏好、社会接触（同性和异性）和性行为，预测增加ER α将减少亲密关系并增加攻击性。

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.