How social challenges prime the brain and body for social instability

描述（由申请人提供）：社会竞争在动物和人类生活中无处不在，来自竞争者的威胁通常会引起类固醇激素睾酮的全身性激增。虽然过去的研究表明社会挑战、睾酮和一系列生理和行为效应之间存在明确的联系，但这些表型变化背后的分子机制却知之甚少。对社会挑战产生适当的有机体反应需要行为和生理的大规模协调（例如攻击性、疼痛耐受性和代谢的变化），然而大脑和身体共同行动以产生对社会挑战协调反应的转录组学机制尚不清楚。这项研究的长期目标是确定类固醇激素如何在基因组和行为反应中连接大脑和周围环境。可行的假设是，社会挑战及其相关的睾丸激素激增，为个体在未来的竞争中取得成功做好了准备，有利于更大程度地调动能量储备，对损伤或炎症的反应增强，以及更强的空间和感官能力，所有这些都是以自我维护为代价的。这一特殊应用的目的是确定攻击性社会互动如何改变基因转录，并描述社会挑战的环境影响在大脑和外围如何不同，同时对社会不稳定产生协调的有机体反应。该主题是一种经过充分研究的鸣禽，其中社会挑战导致睾酮的系统性激增，睾酮对行为和生理的许多方面的影响（攻击，免疫功能，压力，活动等）都得到了很好的表征。通过采用新兴的基因组技术，包括基因集富集和网络共表达分析，拟议的研究将确定(1)急性社会挑战和(2)持续的社会不稳定对基因转录的影响，相对于没有挑战的对照动物。这些数据将揭示基因家族，基因网络中的连接枢纽，以及神经和外周组织，特别容易受到社会诱导的可塑性。组织间的共变异模式将进一步揭示社会挑战使大脑和身体对社会不稳定做出协调反应的精确分子机制。社会压力源如何破坏正常健康的机体功能的知识可以应用于一系列激素和社会诱导的人类健康问题（例如生殖健康，高攻击性行为障碍等），其中通过共同讨论社会环境，大脑和外围获得的见解尚未完全实现。

DESCRIPTION (provided by applicant): Social competition is ubiquitous in both animal and human life, and the threat from a competitor typically induces a systemic surge in the steroid hormone testosterone. While past research demonstrates clear connections among social challenges, testosterone and a suite of physiological and behavioral effects, the molecular mechanisms underlying these phenotypic changes are poorly understood. Generating an appropriate organismal response to social challenges requires large scale coordination of behavior and physiology (e.g. changes in aggression, pain tolerance, and metabolism), yet the transcriptomic mechanisms by which brain and body act together to produce a coordinated response to social challenges are unclear. The long-term goal of the proposed research is to determine how steroid hormones serve to link brain and periphery in genomic and behavioral responses to environmental contingencies. The working hypothesis is that social challenges, and their associated testosterone surges, prime individuals for success in future competition, favoring greater mobilization of energy reserves, heightened response to injury or inflammation, and greater spatial and sensory capabilities, all at the expense of self-maintenance. The objectives of this particular application are to identify how gene transcription is altered by aggressive social interactions, and to characterize how the environmental effects of a social challenge differ in brain and periphery, while engendering a coordinated organismal response to social instability. The subject is a well-studied songbird in which social challenges lead to a systemic surge in testosterone, and the effects of testosterone on many aspects of behavior and physiology are well characterized (aggression, immune function, stress, activity, etc.). By employing emerging genomic techniques, including gene set enrichment and network co-expression analyses, the proposed research will identify the effects of (1) acute social challenges and (2) persistent social instability on gene transcription, relative to unchallenged control animals. These data will reveal gene families, hubs of connectivity within gene networks, and neural and peripheral tissues that are particularly prone to socially induced plasticity. Patterns of co-variation among tissues will further reveal the precise molecular mechanisms by which social challenges prime the brain and body for a coordinated response to social instability. Knowledge of how social stressors derail normal healthy organismal function can be applied to a range of hormonally and socially induced human health issues (e.g. reproductive health, behavioral disorders of high aggression, etc.), where insights to be gained by co-discussion of social environment, brain, and periphery have yet to be fully realized.