CNS Estrogen Receptors and Social Behavior

描述(申请人提供)：重组腺相关病毒(RAAV)载体可用于直接将基因导入细胞，使局部操纵受体成为可能，并可定点改变动物对激素的敏感性。这项研究的目的是利用这项正在开发的技术来增强雄性草原田鼠(Microtus Ochrogaster)的ERα。E会影响男性和女性的各种行为，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，可以利用rAAV来了解类固醇在调节社会行为中的作用。最重要的是，草原田鼠是高度社会性和一夫一妻制的，表现出许多与人类相似的社会互动，使它们成为研究社会行为的更好的啮齿动物模型，而不是老鼠和老鼠等物种。ER基因敲除(KO)小鼠(a和a)的发展为E的作用提供了重要的洞察力，随着rAAV的出现，ER可以在特定的区域被取代，为检验E的影响提供了一个强有力的工具。ERKO小鼠的一个缺点是，它们不仅在成年时缺乏ER，而且在发育过程中也不暴露于E的组织效应。相比之下，草原田鼠受到E的发育影响，但与此同时，至少来自伊利诺伊州的雄性田鼠在BST和MEA中表达很少或根本没有ERα，而且显著低于雌性田鼠。在大鼠和小鼠中，男性和女性的社交互动往往仅限于交配，男性和女性在MeA和BST中都表达高水平的ERα。MEA和BST在调节社会行为方面发挥着重要作用，对草原田鼠与大鼠和小鼠的模式进行比较表明，这些区域缺乏ERa可能是雄性草原田鼠表现出更多社会行为的原因。来自伊利诺伊州的草原田鼠和堪萨斯州的草原田鼠之间的社会行为和ERAlpha的比较进一步支持了这种可能性。伊利诺伊州的草原田鼠是一夫一妻制的，而堪萨斯州的草原田鼠不那么社会化，表现出许多一夫多妻制的特征。雄性KN表现出介于IL草原田鼠和大鼠之间的ERpha模式，KN雄性在BST和MA中表达的ERpha显著多于IL雄性，但在BST中表达低于KN雌性。IL雄性草原田鼠将在BST和MEA中转导rAAV-ERAlpha，并将转染组、假手术组和对照组雄性田鼠进行攻击性、父母行为、伴侣偏好、社会接触(同性和异性)和性行为的测试，预测ERAlpha增加将减少从属关系，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.