Innovative Nursery-Rearing for Improving Rhesus Macaques as Biomedical Models

描述（由申请人提供）：国家研究资源中心（NCRR）的一个主要目标是在NCRR资助的灵长类动物中心维持成功的无特定病原体（SPF）猕猴繁殖计划，这些猕猴不含可能干扰艾滋病实验和其他类型研究的常见逆转录病毒。目前，SPF群体通过在没有非SPF母亲的情况下抚养婴儿来建立。因此，建立和维持这些SPF群体的长期成功的关键是制定有效的策略，以最大限度地减少由于其母亲的社会剥夺而出现的行为病理学，并导致社会能力的发展。这些策略对这些殖民地的长期健康和成功至关重要，原因有二：（1）个体的社会能力对于促进群体中的社会稳定至关重要，这优化了整体群体繁殖成功，以及（2）托儿所饲养的个体与其母亲-同伴饲养的对应个体相比发展不同的心理、生理和免疫反应，这可能会干扰并因此混淆这些动物所分配的研究。两个关键特征似乎对婴儿发展适当的社交和应对技能、最大限度地减少异常行为以及发展适当的生理和免疫系统至关重要：（1）一个适当的和安全的依恋形象，它提供了物种特异性的感官刺激，（2）在与依恋形象的互动过程中，明确的反应-偶然关系（母亲或代理人）和同伴，允许婴儿对他们的环境有一些控制和可预测性和反馈。我们建议利用这两个关键的功能，在开发和测试一套新的托儿所饲养策略，将最大限度地提高应对技能和社会能力的发展，最大限度地减少异常行为，提高在托儿所饲养的SPF恒河猴的生理和免疫效力。拟议的研究将导致发展的互动代理同行养育设计，将提供一个附件的数字，婴儿以及响应应急关系的附件数字（代理）和同行。在早期发育过程中提供这些功能应该会使托儿所养育的婴儿比没有这些功能的托儿所养育的婴儿具有更多正常的社交，运动，知觉和认知技能。被抚养成与母亲同龄人抚养的婴儿更相似的婴儿将为研究人员提供更好的生物医学模型，以及在社会群体中培养更有社会能力的个体，以繁殖后代的SPF动物。这两个结果都解决了三个R中的两个，减少和细化，并提高了个体和整个殖民地的福利。随着作为R24的进一步研究，这项研究可能会导致一种可专利的产品，用于本中心和其他NPRC和灵长类动物设施。这项研究也可能导致重要的基础研究，作为R 01的必要和充分条件所需的正常婴儿的社会，运动，知觉和认知发展，将适用于儿童健康和人类发展。公共卫生相关性：这项拟议研究与人类健康的相关性是双重的。首先，这项研究将导致恒河猴作为生物医学模型的改进，这是灵长类动物中心研究人类健康问题的主要模型。第二，这项研究将导致未来的项目，将直接提高人类健康，通过提供更深入的了解照顾者的功能，这是必要的早期发展，以促进心理健康和幸福的人在整个生命。

DESCRIPTION (provided by applicant): A major goal of the National Center for Research Resources (NCRR) is to maintain successful breeding programs at NCRR-funded primate centers for specific-pathogen-free (SPF) macaque monkeys that are free of common retroviruses that can interfere with AIDS experiments and other types of research. SPF colonies are currently established by raising infants without their non-SPF mothers. Therefore, key to the long-term success of establishing and maintaining these SPF colonies is to develop efficacious strategies for raising infant monkeys in ways which minimize the emergence of behavioral pathologies due to social deprivation of their mothers and which will lead to the development of social competence. Such strategies are crucial to the long-term health and success of these colonies for two reasons: (1) social competence of individuals is critical for promoting social stability in groups, which optimizes overall colony reproductive success and (2) nursery-reared individuals develop different psychological, physiological and immunological responses than their mother-peer reared counterparts, which could interfere with and thus confound the studies to which these animals are assigned. Two key features appear to be most critical for infants in developing proper social and coping skills, minimizing abnormal behavior and developing appropriate physiological and immunological systems: (1) an appropriate and secure attachment figure which provides species specific sensory stimulation and (2) unambiguous response-contingent relationships during interactions with the attachment figure (mother or surrogate) and peers that permit infants some control over and predictability and feedback from their environment. We propose to utilize these two critical features in developing and testing a new set of nursery-rearing strategies that will maximize the development of coping skills and social competence, minimize abnormal behavior and enhance physiological and immunological potency in nursery-reared SPF rhesus macaques. The proposed study will lead to the development of an interactive surrogate-peer rearing design that will provide both an attachment figure to the infant as well as response-contingency relationships with the attachment figure (surrogate) and peers. Providing these features during early development should result in nursery-reared infants with more normal social, motor, perceptual and cognitive skills than nursery-reared infants without these features. Infants raised to be more similar to their mother-peer reared counterparts will provide investigators with a better biomedical model as well as the development of more socially competent individuals in social groups for breeding subsequent generations of SPF animals. Both of these outcomes address two of the three R's, reduction and refinement, and enhances the welfare of the rhesus population both on an individual basis and the colony as a whole. With further research as an R24, this research could lead to a patentable product for use at this and other NPRCs and primate facilities. This research could also lead to significant basic research as an R01 on the necessary and sufficient conditions required for normal infant social, motor, perceptual and cognitive development that would be applicable to child health and human development. PUBLIC HEALTH RELEVANCE: The relevance of this proposed research to human health is two-fold. First, this research will lead to the improvement of the rhesus macaque as a biomedical model which is the leading model at primate centers for investigating human health issues. Second, this research will lead to future projects that will directly enhance human health by providing a deeper understanding of the features of caretakers that are necessary during early development to promote psychological health and well-being in humans throughout life.