CNS Estrogen Receptors and Social Behavior

描述（由申请人提供）：重组腺相关病毒（rAAV）载体可用于直接将基因导入细胞，使受体的局部操作成为可能，并特异性地改变动物对激素的敏感性。本研究的目的是利用该技术提高雄性草原田鼠（Microtus ochrogaster）的erα。E影响多种男性和女性的行为，包括攻击性、隶属关系、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，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化和一夫一妻制的动物，表现出与人类相似的许多社会互动，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）的发展为E的作用提供了重要的见解，并且随着rAAV的出现，ER可以在特定区域被替代，为检查E的影响提供了有力的工具。ERKO小鼠的缺点是它们不仅在成年时缺乏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，草原田鼠受到E的发育影响，但与此同时，雄性（至少来自伊利诺伊州）在BST和MeA中表达erα很少或不表达，且显著低于雌性。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中都表达高水平的erα。MeA和BST在调节社会行为中发挥着重要作用，并且在草原田鼠与大鼠和小鼠中发现的模式的比较表明，在这些区域缺乏erα可能是雄性草原田鼠表现出更多社会行为的原因。通过比较一夫一妻制的伊利诺伊州草原田鼠和一夫多妻制的堪萨斯州草原田鼠的社会行为和er - alpha，进一步支持了这一可能性。大草原田鼠和大鼠的er - α表达模式与大草原田鼠和大草原田鼠相似，大草原田鼠和大草原田鼠的er - α表达明显高于大草原田鼠，而大草原田鼠的er - α表达明显低于大草原田鼠。在雄性草原田鼠的BST和MeA中转染raav - er - alpha，并对转染后的雄性草原田鼠和对照组草原田鼠进行攻击性、亲代行为、伴侣偏好、社会接触（同性和异性）和性行为的测试，预测erα的增加会减少亲缘关系，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.